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    Science & Medicine

    ASCO Guidelines

    ASCO Guidelines Podcast breaks down pivotal recommendations from the latest evidence-based clinical practice guidance and provides insight into daily patient care. Listen to stay up to date with the ever-evolving landscape of cancer research and treatment.

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    Latest Episodes:
    Management of Metastatic Clear Cell Renal Cell Carcinoma Guideline Jun 21, 2022
    Show notes

    An interview with Dr. Tian Zhang from UT Southwester Medical Center in Dallas, TX, author on "Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline." Dr. Zhang reviews the guideline recommendations for the treatment and management of patients with metastatic clear cell renal cell carcinoma and it's implications for clinicians and patients. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines.

    TRANSCRIPT

    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at asco.org/podcasts.

    My name is Brittany Harvey and today I'm interviewing Dr. Tian Zhang from UT Southwestern Medical Center in Dallas, Texas, one of the authors on 'Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline'. Thank you for being here, Dr. Zhang.

    Dr. Tian Zhang: Absolutely. Thank you so much for having me, Brittany.

    Brittany Harvey: Great! First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology.

    Dr. Zhang, do you have any relevant disclosures that are directly related to this guideline topic?

    Dr. Tian Zhang: Yes, I have received past research funding from Novartis, Merck, and Pfizer, as well as advisory board and consulting fees from Merck, Exelixis, Pfizer, BMS, Eisai, and Aveo. All of these industry partners have approved therapies in renal cancer. For the complete list, our audience can refer to the guideline's publication.

    Brittany Harvey: Great, thank you for those disclosures. Then starting off on the content of this guideline, can you give us an overview of the purpose and scope of this guideline?

    Dr. Tian Zhang: Sure. This is a guideline for recommendations for the treatment and management of patients with metastatic clear cell kidney cancer. ASCO gathered 14 colleagues, including myself, that were considered kidney cancer experts from around the world, and we performed a systematic literature review to guide treatment recommendations in metastatic clear cell kidney cancer.

    In the series of ASCO clinical practice guidelines for genitourinary cancers, we hope this guideline will provide recommendations for kidney cancer treatment with supporting data and evidence, particularly given the therapeutic landscape changes since about 2017.

    Brittany Harvey: Then I'd like to review those recommendations that you just mentioned of this guideline. So, this guideline covers six overarching clinical questions. So, I'd like to go question by question for our listeners, starting with how is metastatic clear cell renal cell carcinoma is defined and how is it diagnosed?

    Dr. Tian Zhang: In this portion, we recommended a gold standard of comparing metastatic tissue outside of the primary site to the primary tumor. We discuss adding in staining for PAX8 as well as CA-IX for clarity of clear cell histology.

    The timing is also pretty important in the timing of initial diagnosis and nephrectomy until the appearance of metastatic sites on scans, and radiographic diagnosis is therefore used in settings where prior diagnoses of clear cell kidney cancer has been established and when a metastatic lesion is not accessible for biopsy or when there's clear, measurable disease within a year of the initial diagnosis.

    Brittany Harvey: Understood. And then in the next section of the guideline, what is the role of cytoreductive nephrectomy in metastatic clear cell renal cell carcinoma?

    Dr. Tian Zhang: In this section, we recommend that cytoreductive nephrectomy should be considered for select patients who present with de novo metastatic clear cell kidney cancer to palliate hematuria or pain or to remove the bulk of tumor burden.

    We discuss some past trials in the settings of interferon alpha, and VEGF inhibitors and also recommend consideration of ongoing clinical trials in the era of immunotherapies. There are two such trials that are ongoing, PROBE and Cyto-KIK, that are actively accruing patients.

    Brittany Harvey: Great. And then the guideline goes into options for systemic treatment. So, what are the preferred options for first-line systemic treatment?

    Dr. Tian Zhang: This is probably our most extensive section, as first-line systemic treatments have changed and expanded greatly over the past five years. First, we recommend considering active surveillance for select patients with the following criteria: those who have IMDC favorable or intermediate-risk disease, those with limited or no disease-related symptoms, and also those with a long interval between nephrectomy and the development of metastasis.

    Second, we recommend IMDC risk stratification to then determine treatment selection. Those with IMDC intermediate or poor risk factors should be offered combination treatment with either two immune checkpoint inhibitors or an immune checkpoint inhibitor with an anti-angiogenic VEGF tyrosine kinase inhibitor.

    We provide strong level of evidence with the completed phase three trials in this first-line setting of ipilimumab and nivolumab, axitinib with pembrolizumab, axitinib with avelumab, cabozantinib with nivolumab, and lenvatinib with pembrolizumab.

    For patients with IMDC favorable-risk disease, we recommend an immune checkpoint inhibitor with a VEGF tyrosine kinase inhibitor which may be offered over VEGF TKI alone for those patients who are candidates for immunotherapy.

    In addition, VEGF monotherapy or an immune checkpoint inhibitor monotherapy may be offered for select patients who have certain coexisting medical conditions.

    In addition, we have discussed this long history of high dose interleukin-2 treatments and that this may still be considered in first-line treatments for certain patients while discussing the significant toxicity of IL-2 relative to the newer immunotherapy regimens.

    And finally, we encourage the participation and enrollment into first-line clinical trials when available. A couple of the current ongoing ones include PDIGREE and the LITESPARK-012 Trial.

    Brittany Harvey: I appreciate your reviewing those options and the level of evidence along with those ongoing trials for patients. So, then following those recommendations for first- line that you just went through, what is recommended for the second or later line systemic treatment?

    Dr. Tian Zhang: Subsequent treatment in later lines after initial treatment of refractory renal cell carcinoma depends largely on the initial treatment choices.

    We recommend nivolumab or cabozantinib for patients who had prior progression on a VEGF TKI alone based on the large phase three trials CheckMate 025 and METEOR respectively that gain the approvals for nivolumab and cabozantinib.

    For patients with disease progression on a combination immunotherapy, a VEGF TKI should be considered. Those who progress after initial combination therapy with a VEGF TKI and an immune checkpoint inhibitor should then be offered an alternative VEGF TKI as a single agent.

    And finally, for those who have limited sites of disease progression, local treatment with radiation, thermal ablation, or surgical excision could be offered with continuation of the immunotherapy.

    Brittany Harvey: Thank you for reviewing those second and later line treatment options. So, then following that, what did the panel recommend regarding metastasis-directed therapy?

    Dr. Tian Zhang: There have been some recent studies looking at metastasis-directed treatments, especially for patients with a low volume of metastases. These can include surgical resection, ablation, or radiation therapy. And surgical resection and radiation have not actually been directly compared.

    And so, for those patients, we would recommend a tailoring treatment based on sites of disease. For those patients who do have surgical resection, subsequent VEGF TKIs are not usually recommended based on a prior phase two trial.

    Brittany Harvey: Understood. And then this guideline addresses a couple special subsets of patients. And so, what are those subsets, and what considerations should be applied to the treatment of these special subsets of metastatic clear cell renal cell carcinoma?

    Dr. Tian Zhang: For the special subsets of patients, we considered patients with bone metastases, patients with brain metastases, and also patients with sarcomatoid features on histology.

    For those patients with bone metastases, we recommend bone-directed radiation as well as a bone resorption inhibitor with either a bisphosphonate or a RANK ligand inhibitor.

    We do not have a recommendation on optimal systemic treatments, although given the presence of the MET receptor on bone metastases, regimens containing cabozantinib, which targets the MET receptor in addition to other receptors, may be preferred.

    For those patients who have brain metastases, no definite guidance for treatment can be made given many patients with brain metastases were excluded from the initial trials.

    The overall efficacy of the systemic therapies is low for controlling metastatic kidney cancer in patients with brain metastases. We do recommend local treatment with radiation and or surgery to be undertaken based on the pattern of intracranial metastases. And we refer readers and the audience to a recent guideline from ASCO, ASTRO, and SNO on the management of brain metastases.

    And finally, for patients who have sarcomatoid features on pathology, an immune checkpoint inhibitor-based combination should be chosen in the first line setting. And this is based on multiple phase three trials that have shown improvement in clinical outcomes for patients treated with immunotherapy combinations compared to sunitinib alone.

    Brittany Harvey: Thank you for viewing all these recommendations. The guideline expert panel certainly covered a lot of questions on the treatment and management of metastatic clear cell renal cell carcinoma.

    So, then in your opinion, Dr. Zhang, what is the importance of this guideline and how does it impact clinicians?

    Dr. Tian Zhang: Sure. You know, in the past 10 years, our treatment options for metastatic kidney cancer have greatly expanded and multiple options are now available. For busy clinicians who may not treat kidney cancer, especially in the metastatic setting often or on a routine basis, this set of guidelines provides a high-level approach to the common management scenarios that clinicians are often faced with.

    My fellow committee members and I hope that these guidelines will provide a comprehensive one-stop document that is relevant and updated for the busy clinician taking care of patients with metastatic kidney cancer.

    Brittany Harvey: Great! And then finally, how will these guideline recommendations affect patients with metastatic clear cell renal cell carcinoma?

    Dr. Tian Zhang: The fact that our treatment options for metastatic kidney cancer have improved clinical outcomes, including extending the time until progression as well as overall survival, is truly wonderful news for patients who are diagnosed with metastatic kidney cancer today.

    If patients are directly reading these guidelines, they can also see whether overall recommendations align with their recommended course of treatment, with the caveat that every patient's care is tailored to them based on coexisting medical conditions and concurrent medications. But we hope these guidelines will be helpful for all of our patients.

    Brittany Harvey: Yes, it's great to see improved clinical outcomes for patients. So, I want to thank you for all of your work on this guideline and for taking the time to review the guideline recommendations and its impact.

    Dr. Tian Zhang: Sure. I really appreciate ASCO giving this time and opportunity, Brittany, and also the audience for their interest in the clinical guidelines for metastatic clear cell renal cell carcinoma.

    Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series.

    To read the full guideline, go to www.asco.org/genitourinary-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

    Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.


    Systemic Therapy for Melanoma Rapid Recommendation Update Jun 03, 2022
    Show notes

    An interview with Dr. Pauline Funchain from Cleveland Clinic in Cleveland, OH, author on "Systemic Therapy for Melanoma: ASCO Guideline Rapid Recommendation Update." Dr. Funchain reviews recent evidence and updated recommendations from the ASCO Expert Panel for the use of tebentafusp in patients with metastatic uveal melanoma. For more information, visit www.asco.org/melanoma-guidelines.

    TRANSCRIPT

    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at asco.org/podcasts.

    My name is Brittany Harvey and today I am interviewing Dr. Pauline Funchain from Cleveland Clinic in Cleveland, Ohio, author on Systemic Therapy for Melanoma: ASCO Guideline Rapid Recommendation Update. Thank you for being here, Dr. Funchain.

    Dr. Pauline Funchain: It's great to be here with you, Brittany. Thank you!

    Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline.

    The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology.

    Dr. Funchain, do you have any relevant disclosures that are directly related to this guideline topic?

    Dr. Pauline Funchain: I do not have relevant disclosures that relate to this guideline topic.

    Brittany Harvey: Great, thank you. Then getting into the rapid update, what prompted this rapid update to the Systemic Therapy for Melanoma: ASCO Guideline published in 2020?

    Dr. Pauline: So, earlier this year, on January 25th, the FDA approved tebentafusp for metastatic uveal melanoma. So, this is the first FDA approval for metastatic uveal melanoma. We felt it was really important to put out a rapid update to let both clinicians know about the therapy and also so that more patients can get access to it as quickly as possible.

    Brittany Harvey: Understood. So, then based on this new FDA approval, what are the updated recommendations for patients with uveal melanoma?

    Dr. Pauline Funchain: So, any patients who have a previously untreated metastatic uveal melanoma, and also who are HLA-A*02:01 positive, this group of patients should be offered tebentafusp as systemic therapy.

    This is the only systemic therapy that has been shown to prolong overall survival in patients with metastatic uveal melanoma. And if you look at the kind of benefit that was seen, patients who were on tebentafusp had a median overall survival of 21.7 months versus 16 months in comparison to investigator's choice. In this case, that was either single agent pembrolizumab, ipilimumab, or dacarbazine. So, it is a pretty significant overall survival benefit.

    Brittany Harvey: Great! Thank you for reviewing those updated recommendations and the data behind them. So, what should clinicians know as they implement this updated recommendation?

    Dr. Pauline Funchain: So, they should know that there was a great overall survival benefit seen, but it doesn't correlate with the objective response rate that was seen in the trial. So, for patients who were treated with tebentafusp, the objective response rate was 9%. And for those patients who were treated with the investigator's choice, again, that was single agent pembrolizumab, ipilimumab, or dacarbazine, the response rate was 5%.

    So, that margin was not very different in terms of objective response rate when looking at RECIST-based criteria, so radiologic criteria for response, but the survival was clearly seen. And interestingly, even in those patients that had radiologic progression, there was an improved survival for those patients who were on tebentafusp versus investigator's choice.

    So, there is some kind of survival benefit that may not correlate with what is seen on imaging. So, clinicians should know that they may not see a dramatic response in terms of tumor size on imaging, but patients may still benefit from the therapy.

    Brittany Harvey: Understood. So, then you've just talked a little bit about responses in patients. So, how does this guideline update affect patients with melanoma?

    Dr. Pauline Funchain: So, despite a difference in response rate, long story short, there is an overall survival difference. So, really, this is the first overall survival difference that we have seen in metastatic uveal melanoma.

    It is really exciting. It is finally an approved drug for metastatic uveal melanoma, which did not have any approved or standard of care, systemic drugs. So, this is a really big win for a rare disease. I think, in terms of the general melanoma field and also the cancer field in general, this is really an exciting first-in-class drug on two different fronts. It is the first approved T-cell receptor therapy. It is also the first bispecific protein and it works differently than other immunotherapies we have seen. So, hopefully, this is something we see more of in other cancers.

    Brittany Harvey: Definitely, it's good to see that these patients finally have an option and we'll look forward to research in other cancers as well. So, then finally, Dr. Funchain, what are the outstanding questions regarding systemic therapy for melanoma?

    Dr. Pauline Funchain: Well, there are multiple questions that are outstanding. I think, for metastatic uveal melanoma, I think there are a lot of questions about the dissociation between the radiologic response and survival. I think there are questions about knowing when to stop tebentafusp if it's not working because we don't really have a good sense of what we should be using to know if this is not the right therapy for that patient.

    I think we would love to know what the biomarkers of response are, and we may need different ways of looking for how to judge if a patient is benefiting from tebentafusp and other systemic therapies. And I think that there's still a big question in uveal melanoma about whether we start with systemic therapy or local therapy. I don't think that's been answered.

    Now, in terms of the entire guideline, I think for melanoma in general, there are new data that are emerging and have been recently published and we will be looking forward to the next ASCO guideline in systemic therapy for melanoma because I think that there are a lot of emerging data that need to be addressed.

    Brittany Harvey: Definitely. We'll look forward to that new research in uveal melanoma and to reviewing the updated data with the guideline panel for the next edition of the systemic therapy for melanoma guideline. So, I want to thank you so much for your work to rapidly updating this guideline, and thank you for your time today, Dr. Funchain.

    Dr. Pauline Funchain: Thank you for having me. It is really meaningful to us to be able to offer education and get the word out about therapies that can help our patients.

    Brittany Harvey: Agreed. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. To read the full rapid recommendation update, go to www.asco.org/melanoma-guidelines.

    You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

    Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.


    Management of Advanced HER2-Positive Breast Cancer and Brain Metastases Guideline Update May 31, 2022
    Show notes

    An interview with Dr. Naren Ramakrishna from Orlando Health Cancer Institute in Orlando, FL, and Dr. Carey Anders from Duke University in Durham, NC, co-chairs on "Management of Advanced Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer and Brain Metastases: ASCO Guideline Update." This guideline reviews evidence in both the local therapy management and systemic therapy management for patients with HER2-positive breast cancer and brain metastasis, and provides updated recommendations for these patients. Read the full guideline at www.asco.org/breast-cancer-guidelines.

    TRANSCRIPT

    Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts.

    My name is Brittany Harvey, and today I'm interviewing Dr. Naren Ramakrishna from Orlando Health Cancer Institute in Orlando, Florida. And Dr. Carey Anders from Duke University in Durham, North Carolina, co-chairs on 'Management of Advanced Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer and Brain Metastases: ASCO Guideline Update'. Thank you for being here. Dr. Ramakrishna and Dr. Anders.

    Dr. Carey Anders: Thank you.

    Dr. Naren Ramakrishna: Thank you.

    Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology.

    Dr. Ramakrishna, do you have any relevant disclosures that are directly related to this guideline topic?

    Dr. Naren Ramakrishna: No.

    Brittany Harvey: And Dr. Anders, do you have any relevant disclosures that are directly related to this guideline topic?

    Dr. Carey Anders: I do. I would just like to disclose that I receive research funding, compensated consulting roles, and royalties from several of our industry partners who are developing brain permeable compounds.

    Brittany Harvey: Thank you. Let's talk about the content of this guideline. So, Dr. Anders, what prompted an update to this guideline? And what is the scope of this guideline update?

    Dr. Carey Anders: Thank you for that question, Brittany. Our previous guideline in the management of HER2-positive breast cancer brain metastasis was published in 2018. And since that time, we've seen significant progress in both the local therapy management and systemic therapy management for our patients with HER2-positive breast cancer and brain metastasis.

    I think collectively, this body of work really prompted the panel to think through the changes that we could make to improve the care of our patients taking these updates into account. I'd love to hear Dr. Ramakrishna's take on the rationale for the update as he was also involved in the 2018 guideline.

    Dr. Naren Ramakrishna: Thank you, Carey. Well, it's really an exciting time right now for breast cancer brain metastasis treatment. And the recent data that Dr. Anders referred to has really opened up a whole new era in terms of therapeutic possibilities for breast cancer brain metastasis patients.

    In the past, we've relied on traditional methods of treatment like whole-brain radiotherapy, surgery, and stereotactic radiosurgery as mainstays of treatment. But this exciting data that Dr. Anders referred to, has resulted in the possibility of avoiding certain of the local therapy options in select patients, which has the potential to increase patient survival and quality of life, and is a major advancement.

    Brittany Harvey: Excellent. It's great to hear about those advancements. So, then next, I'd like to start by reviewing the guideline recommendations for our listeners. Dr. Ramakrishna, what are the key recommendations for local therapy for patients with HER2-positive breast cancer and brain metastases?

    Dr. Naren Ramakrishna: Since the 2018 updated guidelines, we've continued with our stratification of patients by prognosis by the number of metastases, size of metastases, and also whether they are symptomatic or asymptomatic.

    Overall, the changes include the offering of systemic therapy for patients after multidisciplinary review for asymptomatic metastases, particularly those less than two centimeters in size. In select cases, one might also offer it for patients with metastases larger than that.

    The other major change that we see in this update is an increasing reliance on stereotactic radiosurgery rather than whole-brain treatment as a local therapy option, both in the post-operative setting and for single or multiple metastases, for which surgery is not recommended.

    Finally, we see a significant change in the application of whole brain radiation, where whole-brain radiation is recommended typically for extensive disease, either with multiple, very large metastases, or many, many small metastases. We recommend whole brain treatment to always be administered with a neuroprotectant, and where possible, with what's called hippocampal sparing, which is thought to reduce the neurocognitive negative effects of whole-brain radiation treatment.

    Brittany Harvey: Understood, I appreciate those recommendations for local therapy and that overview that you provided. So then Dr. Anders, in addition to those recommendations, what are the key recommendations for systemic therapy for these patients?

    Dr. Carey Andres: Sure, Brittany, happy to review. I think some of the general principles from the 2018 guidelines remain in place. So, for instance, our patients who have progressive disease in the brain, are eligible for local therapy and have controlled extracranial disease, we still recommend continuing the current HER2-directed therapy along with the same algorithm for the treatment of patients with HER2-positive metastatic breast cancer.

    There are some interesting and exciting changes to the guidelines with the advent of several of the promising systemic therapies that Dr. Ramakrishna outlines such that we do have the option of leading with systemic therapy for our patients with small asymptomatic lesions in the brain predominantly based on the HER2CLIMB clinical trial which established tucatinib, capecitabine and trastuzumab in this setting.

    So, in concert with our local therapist, we have the consideration for moving to the HER2CLIMB regimen in the setting of active asymptomatic brain metastasis in concert with our local therapist. So, that's one key change from the 2018 guidelines.

    Another is the introduction of the compound trastuzumab deruxtecan, an antibody-drug conjugate, which has been shown in second line in the setting of metastatic HER2-positive breast cancer to be superior to our traditional T-DM1 therapy in this setting.

    In the study, the Destiny-Breast03 study that illustrated the superiority of trastuzumab deruxtecan patients with stable brain metastasis were included and illustrated in this compound, illustrated significant benefit for patients with stable brain metastasis.

    So, in addition to the HER2CLIMB regimen in the setting of stable brain metastasis, we also have the option of trastuzumab deruxtecan in this setting. And that was an update in our 2022 guidelines.

    So, we essentially have more systemic therapy tools in our toolkit to consider in concert with local therapy. And I just want to emphasize the importance of communication between the systemic therapy team and the local therapy teams, particularly when we're making the decision to move forward with the systemic therapy in the setting of progressive or stable brain metastasis.

    Brittany Harvey: Thank you. Yes, that multidisciplinary care is key, and I appreciate your reviewing those updates. So then, in addition to those what is recommended regarding screening for the development of brain metastases for patients with HER2-positive breast cancer?

    Dr. Carey Andres: So, this is a very active conversation. And in fact, I had this very conversation with two patients in the clinic just yesterday. So, should we be screening our patients with advanced HER2-positive breast cancer with brain MRIs in the absence of symptoms? I think the bottom line is we just don't have the data yet. I think we will have the data and in fact, there are ongoing prospective studies trying to determine whether or not screening brain MRIs in the absence of symptoms in this setting will improve our patient survival, and also improve our patients' quality of life.

    Until we have that data because we do have these new tools in the toolkit for systemic therapy treatment, the panel loosens the guidelines a bit to say that it's not that we no longer recommend screening in the asymptomatic state, but there's not enough data for or against. And I think this really will help the physician and patients as they're making decisions about their screening and restaging studies in a personalized manner.

    In addition to the lack of data, we also strongly recommend that clinicians and patients have a very low threshold to obtain a brain MRI in the presence of symptoms and this is really important with regards to communication about symptoms as subtle as they may be. I'd love to hear Dr. Ramakrishna's take on this challenging space where we clearly need more data.

    Dr. Naren Ramakrishna: Yes, Carey, I completely agree that it's quite challenging and the practice patterns are quite diverse throughout the country. It's also a source of a great deal of apprehension and anxiety for patients who automatically typically would assume that more frequent screening is better, especially when they do develop brain metastasis if that's to occur.

    So, we do look forward to better data for guidance. And it certainly is an area that should undergo multidisciplinary reviewing recommendations for any particular patient.

    Brittany Harvey: Understood, thank you both for reviewing the evidence as it states now and we'll look forward to that emerging data for perhaps a future guideline update. So then, Dr. Ramakrishna, what in your view is the importance of this guideline update and what does it mean for clinicians?

    Dr. Naren Ramakrishna: Well, this is a practice-changing update. I mean, I don't think that's an overstatement. Because for the first time, upfront therapy is going to include the possibility of systemic therapy. And this also means that there has to be multidisciplinary and multimodality discussions regarding local versus systemic therapy for a large proportion of HER2-positive breast cancer brain metastasis patients. So, practice patterns are going to shift as a result of the incorporation of systemic therapy into the treatment paradigm.

    And finally, the other very important, practice-changing local therapy change is that the use of whole-brain treatment will be reduced relative to stereotactic radiosurgery, but in some cases, also as a result of the use of systemic therapy, and when it is employed, it must be utilized with a neuroprotectant and/or hippocampal sparing.

    Brittany Harvey: Great and then finally, how will these guideline recommendations affect patients with HER2-positive metastatic breast cancer and brain metastases?

    Dr. Carey Andres: So, I would just echo Dr. Ramakrishna's comments about the advances that we've seen and the importance of multidisciplinary care. I think from a systemic therapy perspective, we have the wonderful problem of having multiple agents to consider in this space. And as we've seen, really an explosion of HER2-directed therapies that are now approved and available to patients. One of our challenges has been how to sequence these therapies.

    And so, we were hopeful that these guidelines will help clinicians and patients determine when to pick individual regimens that best fit the patient's scenario, whether or not their brain metastases are stable at that decision tree, or whether or not they're progressive at that decision tree.

    I would also point the listeners to the updated guidelines in the management of patients with HER2-positive metastatic breast cancer, as these guidelines will certainly complement the decision-making and systemic therapy, incorporating the presence or absence of brain metastasis.

    Brittany Harvey: Great, and yes, thank you for highlighting that companion guideline. Both are available at asco.org/breast-cancer-guidelines and in the Journal of Clinical Oncology.

    So, I want to thank you both so much for your work on these guidelines and for taking the time to speak with me today, Dr. Anders and Dr. Ramakrishna.

    Dr. Naren Ramakrishna: Thank you very much, Brittany.

    Dr. Carey Andres: Thank you! Thanks for the opportunity.

    Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. To read the full guideline go to www.asco.org/breast-cancer-guidelines.

    You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

    Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.


    Systemic Therapy for Advanced HER2-Positive Breast Cancer Guideline Update May 31, 2022
    Show notes

    An interview with Dr. Sharon Giordano from the University of Texas MD Anderson Cancer Center in Houston, TX, and Dr. Nancy Davidson from Fred Hutchinson Cancer Research Center and the University of Washington in Seattle, WA, co-chairs on "Systemic Therapy for Advanced HER2-Positive Breast Cancer: ASCO Guideline Update." This guideline updates recommendations on systemic therapies for advanced HER2-positive breast cancer, focusing on second-line, third-line, and greater treatment. Read the full guideline. TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Sharon Giordano from the University of Texas MD Anderson Cancer Center in Houston, Texas, and Dr. Nancy Davidson from Fred Hutchinson Cancer Research Center and the University of Washington in Seattle, Washington, co-chairs on 'Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer: ASCO Guideline Update'. Thank you for being here. Dr. Giordano and Dr. Davidson. Dr. Sharon Giordano: Thank you. Dr. Nancy Davidson: Thank you for having us. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Giordano, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Sharon Giordano: No, I do not. Brittany Harvey: Thank you. And Dr. Davidson, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Nancy Davidson: No, I do not. Brittany Harvey: Thank you. Let's talk about the content of this guideline update. So first, Dr. Giordano, what prompted an update to this guideline on the systemic therapy for advanced HER2-positive breast cancer, and what is the focus of this update? Dr. Sharon Giordano: So, we were prompted to update the guidelines for HER2-positive metastatic breast cancer because several new studies have been presented and published, which are really changing our standard of care approaches. We have new therapies and new combinations that have resulted in improvements in progression-free survival and in overall survival for this patient population. Given the clinical importance of these new studies, we felt that an update of the treatment guidelines was clearly needed. Overall, the focus of our update is really in the title, so, it's systemic therapies for advanced HER2-positive breast cancer. And specifically, what we're focusing on is updating the recommendation for second-line therapy, and then adding multiple new options for systemic therapies for third-line and greater treatment. Brittany Harvey: Great. Thank you for that overview. So, then I'd like to review the updated recommendations of this guideline for our listeners. Starting with, Dr. Davidson, what is recommended for first-line therapy for patients with advanced HER2-positive breast cancer? Dr. Nancy Davidson: So, that was the part of this guideline that really did not change. In the previous iteration and in the current iteration, we felt that the evidence suggested that a combination of trastuzumab and a taxane should be the first-line treatment for individuals with metastatic HER2-positive breast cancer unless they have some sort of contraindication to the taxanes. Now, the evidence supporting that is very strong. The trial that supported this continues to be updated and continues to show benefit. So, that's a very high level of evidence and our recommendation on this was extremely strong. Brittany Harvey: Great. And then following those first-line recommendations, Dr. Giordano, what is recommended for second-line treatment for these patients? Dr. Sharon Giordano: So, we did change our recommendation for second-line treatment for HER2-positive patients. The current new recommendation is, and I quote from our guideline, "If a patient's HER2-positive, advanced breast cancer has progressed during or after first-line HER2 targeted therapy, and the patient has not received trastuzumab deruxtecan, clinicians should recommend trastuzumab deruxtecan as a second-line treatment." So, as I said before, this recommendation is a change from our prior second-line recommendation. Previously, we had recommended T-DM1. So, this change was really, I think, one of the most important changes to the guidelines with this update. We made the recommendation based on the initial presentation of the results of the Destiny-Breast03 trial, really given the magnitude of the benefit that was seen in the study. And the manuscript I would note was published this month in the New England Journal of Medicine. Overall, the study showed statistically significant and highly clinically meaningful reduction in progression-free survival. So, just to give you some of these numbers, to kind of give you a sense of how big the impact was, so 76% of patients who were treated with trastuzumab deruxtecan versus 34% of patients treated with trastuzumab emtansine were alive and without disease progression at a year, with a hazard ratio of 0.28. The response rates are also quite impressive with 80% versus 34% response rates. And the overall survival data are still immature but do favor treatment with trastuzumab deruxtecan and that hazard was 0.55. So, I will note though, that toxicity was a bit higher with the new drug, with trastuzumab deruxtecan. So, any grade adverse events were 98% versus 87%. And then if you look at grade three and four drug-related adverse events, it was 45% versus 40%. I think of note, rather than just kind of the overall numbers, though, one thing that clinicians need to be aware of is the risk of interstitial lung disease with this new drug. And this occurred in about 10% of treated patients in this study, although only 1%, or I think it was two patients, who had grade three or higher pulmonary toxicity. So, this is a toxicity that is specific to this drug that clinicians do need to be aware of. Dr. Nancy Davidson: I think the other thing on that, Sharon, is that the incidence was lower in the Destiny Breast03 trial than it had been in some of the really early studies of this agent, so, that should be reassuring to us. Although, of course, it doesn't mean that the side effect doesn't happen, you have to take note of it. Dr. Sharon Giordano: That's a great point. It definitely was lower than we'd seen before. So, a little bit of a relief, but still there. Brittany Harvey: Great, thank you both for reviewing that data. I appreciate the overview. So then, following those recommendations for second-line treatment, Dr. Davidson, what are the recommended options for third-line therapy for patients with HER2-positive advanced breast cancer that has progressed on second-line or greater HER2 targeted therapy? Dr. Nancy Davidson: Well, of course, this is the area where there has been considerable change as well. And that's because of the wealth of new anti-HER2 agents that Dr. Giordano talked about earlier. So, we had a variety of recommendations for clinicians and patients to make decisions about how to proceed. I think certainly one of them, is that if the patient did not receive trastuzumab emtansine (T-DM1) in the second line, as we just talked about, our new recommendation would be that they would not, that they would receive trastuzumab deruxtecan, so you put off for T-DM1 in that [third-line] setting. And that's a new recommendation for us. And the strength of the recommendation is quite high. Another agent that's come along that's very exciting is tucatinib, one of the small molecule inhibitors. And we think that that is also an alternative, that tucatinib in combination with trastuzumab and capecitabine, again, nice activity and pretty strong recommendation based on analyzed critical trials. And then finally, if for some reason the patient didn't receive the trastuzumab deruxtecan in a second-line setting and you're now in the third-line setting, that would be a very reasonable agent for them as well. Those are all pretty strong recommendations. And I think the choice of which to proceed will depend a little bit on the decision making between the patient and the doctor about the mode of administration, your side effect profile, what seems the most appropriate, and it might be more one of the order of the recommendation. As opposed to saying, 'This one, but not that one', it might be, 'Pick this one next and know that you will be able to return to some of these in the future.' Now, there are a lot of other possibilities here. We already had available to us neratinib and capecitabine, that continues to be part of the portfolio. And we also had lapatinib and capecitabine, also part of the portfolio. Other combinations of chemotherapy, trastuzumab could be considered, a new agent called margetuximab with chemotherapy, which has also come on to the market. And of course, there's the possibility of thinking about the anti-HER2 agents in the context of endocrine therapy for those patients who have estrogen receptor-positive breast cancer as well. And new information suggesting that you might, in some cases, even think about one with CDK 4/6 inhibitors in the context of trastuzumab and fulvestrant. So, lots of possibilities here that patients and doctors can weigh, and again think about order of administration as opposed to selecting for or against the other. I do think that the leading contenders at the beginning are going to be T-DM1 or trastuzumab deruxtecan, if that hasn't been used, or tucatinib in combination, those would be my personal preferences. Brittany Harvey: Great. Thank you for reviewing those options and describing where a patient might receive these during their treatment. Dr. Nancy Davidson: I'd like to hear Dr. Giordano's thoughts on that, how would you stack those up? Dr. Sharon Giordano: Yeah, well, as you said, I think it does depend on what the patient's been treated with previously. I mean, certainly, T-DM1 or trastuzumab deruxtecan, if they haven't had those agents. Otherwise, I think the data from the tucatinib trastuzumab capecitabine regimen is pretty impressive as it did show an overall survival benefit. And as you know, I think that regimen is also really interesting, because it does seem to have some efficacy for patients with brain metastases. That actually has a very nice advantage. Then the other ones, I think it just sort of depends on what they've seen previously, what side effects they may be experiencing, and kind of other quality of life issues. I don't see that there's a clear way to sequence the other ones since most of them haven't really been directly compared head-to-head against each other. Brittany Harvey: It seems like it may be an individual discussion between clinicians and patients at that level. So, then, Dr. Giordano following that, how will this guideline impact clinicians and what should they know as they implement these updated recommendations? Dr. Sharon Giordano: I think the bottom line is really the clinicians are now going to have more options for the treatment of HER2-positive advanced breast cancer which is fantastic news to have all these different choices and options for our patients. To me, I think probably the most important changes and recommendations, again, are the addition of trastuzumab deruxtecan in the second-line setting just given the very impressive clinical benefit that's seen with that drug, or, as Nancy mentioned in the third-line setting if patients, for some reason haven't received it previously. And then I also think, as we talked about, the tucatinib combination is really an exciting new combination that does seem to have significant clinical benefit. I think the clinicians will need to be aware that that might be an option for patients with CNS metastases that are progressing. And also, just to be aware, as we mentioned before, about the risk of the interstitial lung disease with trastuzumab deruxtecan but it's really encouraging to me to have such a long list of drugs and combinations that we can use to treat our patients. Brittany Harvey: Excellent. Those are great points. So, then finally, to wrap us up, Dr. Davidson, in your view, how will these guideline recommendations impact patients with advanced HER2-positive breast cancer? Dr. Nancy Davidson: Well, Brittany, I think one thing we hope, of course, is that those patients will cumulatively have a longer survival, and a better survival as a consequence of all of these new insights that we've been able to make. I can imagine it would be maybe a little confusing to patients that there are so many things that they might potentially be able to choose from, but this is one where I think that the larger the panel of agents that you have available to you, the happier it is. So, I hope that patients are going to look at this as an opportunity for partnership with their oncologists to try to figure out of all these possibilities, what's the best one for me now, and they're going to have the comfort of knowing that there'll be other things that they can fall back on in the future, and that, hopefully, these things will improve outcomes. And again, without excessive toxicity. This last thing I'm going to hope that clinicians and physicians will remember is that we've made a lot of headway here, but that our results are not perfect. And so, right now, we're able to change guidelines, these guidelines today because of clinical trials that have been put together in the last several years and successfully implemented. And I hope that we're going to continue to do that because until we get to a point where survival from HER2-positive breast cancer is 100%, we've got work to do. So, they're going to be other new clinical research strategies, and I hope that doctors and patients will take advantage of those whenever possible. Brittany Harvey: Absolutely, both hoping for longer survival and better quality of life and looking forward to more clinical trials to give clearer answers. I want to thank you both so much for your time today and for all of your work on updating these guideline recommendations, Dr. Davidson and Dr. Giordano. Dr. Nancy Davidson: Thanks, Brittany. Dr. Sharon Giordano: Thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guideline Podcast Series. To read the full guideline go to www.asco.org/breast-cancer-guidelines. There's a companion guideline update on the management of advanced HER2-positive breast cancer and brain metastases also just published in the Journal of Clinical Oncology and on asco.org. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines App available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast expressed their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of AS…

    Full show notes at the publisher

    Exercise, Diet, and Weight Management During Cancer Treatment Guideline May 16, 2022
    Show notes

    An interview with Dr. Jennifer Ligibel from Dana Farber Cancer Institute in Boston, MA and Dr. Catherine Alfano from Northwell Health Cancer Institute and Feinstein Institutes for Medical Research in New York, NY, co-chairs on "Exercise, Diet and Weight Management During Cancer Treatment: ASCO Guideline." This guideline addresses recommendations for exercise, diet, and weight management for adult patients undergoing active cancer treatment, highlighting where there is evidence to recommend interventions, and where future research is needed. Read the full guideline at www.asco.org/supportive-care-guidelines.

    TRANSCRIPT

    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at asco.org/podcasts.

    My name is Brittany Harvey, and today I'm interviewing Dr. Jennifer Ligibel from Dana Farber Cancer Institute in Boston, Massachusetts, and Dr. Catherine Alfano from Northwell Health Cancer Institute, and Feinstein Institutes for Medical Research in New York, New York, co-chairs on 'Exercise, Diet and Weight Management During Cancer Treatment: ASCO Guideline'.

    Thank you for being here, Dr. Ligibel and Dr. Alfano.

    Dr. Jennifer Ligibel: Thanks for having us.

    Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline.

    The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Ligibel, do you have any relevant disclosures that are directly related to this guideline topic?

    Dr. Jennifer Ligibel: I have no personal conflicts with this guideline.

    Brittany Harvey: Thank you. Dr. Alfano, do you have any relevant disclosures that are directly related to this guideline topic?

    Dr. Catherine Alfano: I have no conflicts.

    Brittany Harvey: Thank you. Then, getting into the content of this guideline. Dr. Ligibel, can you start us off with an overview of the scope of this guideline?

    Dr. Jennifer Ligibel: Sure. So, this guideline was developed to provide recommendations around exercise, diet, and weight management for patients undergoing active cancer treatment. We defined active cancer treatment as either the perioperative period or the period of time in which patients were receiving chemotherapy and/or radiation.

    This guideline specifically focuses on adult cancer patients and largely focuses on individuals undergoing treatment for curative intent. There were a number of reasons why we thought it was important to develop a guideline specifically for patients who were undergoing cancer treatment.

    There are a number of other guidelines that talk about the role of these types of lifestyle factors in preventing cancer, and also information widely available about the potential benefits of exercising more, consuming certain types of diets, or losing weight after cancer treatment is finished. But there's much less information about the feasibility and potential benefits and safety of increasing your exercise, changing your diet, or losing weight during cancer treatment.

    This is the time when oncology providers are primarily working with patients in a time when patients have a lot of questions about what they should be eating and what they should be doing. So, this guideline was developed to specifically try to provide guidance during treatment.

    Brittany Harvey: Yes, definitely an area in which guidance is very much needed. So, then Dr. Alfano, I'd like to next review the key recommendations of this guideline, starting with what are the recommendations regarding exercise during cancer treatment?

    Dr. Catherine Alfano: For exercise, the expert panel felt that the evidence was very strong. And so, oncology providers should recommend aerobic and resistance exercise during active treatment with curative intent because it can mitigate the side effects of cancer treatments.

    So, exercise has been shown during active cancer treatment to reduce fatigue, to either improve or preserve a patient's cardiorespiratory fitness, their physical functioning, their strength outcomes, and in some kinds of patients exercise has been shown to improve quality of life and reduce anxiety and depression.

    The evidence is not sufficient to recommend exercise specifically for improving cancer control outcomes yet. This is a source of ongoing study, but we felt that the evidence was strong enough that oncology providers should recommend aerobic and resistance exercise, and it should become the standard of care for all cancer patients.

    The second recommendation regarding exercise is that oncology providers may recommend pre-operative exercise for patients specifically undergoing surgery for lung cancer. So, this can be called prehab or pre-habilitation exercise. And this exercise has been shown to reduce outcomes like the length of hospital stay and postoperative complications.

    Brittany Harvey: Excellent. Thank you for reviewing those recommendations and the level of evidence behind them. So, then, Dr. Ligibel, what did the panel recommend regarding particular dietary patterns or foods for patients during cancer treatment?

    Dr. Jennifer Ligibel: One of the things that we recognized as a panel as we reviewed the evidence that shaped these guidelines was that there was much less evidence for both dietary factors and whether that was specific dietary patterns or some specific foods, as well as weight management, how those types of changes during treatment, affected outcomes, or even the feasibility of changing your diet or losing weight during cancer treatment. We, for this guideline, really relied on randomized trials to help shape our guidance, and we realized very quickly that there were few randomized trials testing dietary change or weight management during cancer treatment.

    So, as a panel, we debated for a long time about what we should say in this setting. We did find that there were a few randomized trials that specifically looked at neutropenic diets. We defined that as diets that omitted fresh fruits and vegetables for patients who had undergone treatment for hematologic malignancies, and in particular bone marrow transplants.

    Those studies were designed to look at whether those types of diets reduce the risk of infection. We did not see evidence that omitting fruits and vegetables during cancer treatment for those malignancies, reduced infection, and so the group provided a recommendation that neutropenic diets not be recommended for patients during cancer treatment, but we were unable to provide specific guidance regarding other dietary factors or the incorporation of specific foods during cancer treatment.

    As a group, we recognize the importance of a healthy diet for general health. But given that we were really looking at randomized trials of the effects of changing someone's diet during treatment, we ultimately did not make a recommendation for a particular diet during cancer treatment, but really called for more research with well-designed clinical trials to test the impact of things like plant-based diets, intermittent fasting, other types of diets for which there may be interesting preclinical evidence, but very little information in people about the benefits or even the safety of these types of diets during cancer treatment.

    Brittany Harvey: Understood, I appreciate you outlining the nuance of that recommendation, and also the areas for future research, which we can get into a little bit more in a little bit. So then, in the last category of recommendations, Dr. Alfano, what does the guideline state regarding interventions to promote intentional weight loss or avoidance of weight gain during cancer treatment?

    Dr. Catherine Alfano: So, when our panel reviewed the evidence for weight loss or the avoidance of weight gain during cancer treatment, unfortunately, we decided that ultimately, there's insufficient evidence right now to recommend either for or against intentional weight loss or the prevention of weight gain during active treatment to improve outcomes related to the quality of life or things like treatment toxicities, or ultimately cancer control outcomes.

    Brittany Harvey: Thank you, Dr. Alfano, for that recommendation, as well. So, Dr. Ligibel, in your view, what is the importance of this guideline? And how will it impact both clinicians and patients?

    Dr. Jennifer Ligibel: This guideline is really the first large-scale effort to pull together all of the data from randomized trials about the effects of changing your lifestyle, exercising more, in particular, changing your diet, changing your weight during cancer treatment.

    I think that as a panel, we found very clear and consistent evidence as Dr. Alfano outlined, that exercise has concrete benefits for patients during cancer treatment. I think that this is really an important call to action, both for providers in speaking about these topics to their patients, but also for payers. And as we think about our healthcare system, about how we're going to support patients in becoming more active in a safe way during their cancer treatment.

    I think that it's very important that we recognize that encouraging physical activity is not just telling people that they should go out and do it. We really need to think about how we support patients in making these types of lifestyle changes in a sustained way.

    So, I think that this guideline really provides clear evidence that exercise is important. It also provides clear evidence that we need more research in other areas. Patients are asking their oncology providers every day, what they should be eating, whether they should be thinking about losing weight, and we really don't have clear evidence to guide these conversations at this point.

    I do think it's important to recognize that as a panel, we all felt very strongly that this guideline should not be interpreted as saying that a healthy diet or maintaining a healthy weight during treatment wasn't important. But we were really struck by the dearth of high-level evidence to be able to help our patients make informed choices and I think that's something that, from this guideline, we really need to come up with a plan be better able to ask the question that comes up in the clinic every day of, 'Doctor, what should I eat?'

    Brittany Harvey: Those are excellent points. I appreciate the panel looking critically at the evidence that's actually out there to try and determine recommendations. So then, Dr. Ligibel just mentioned a few areas in which more research is needed. So, Dr. Alfano, what are the outstanding questions regarding optimal diet, weight management, and exercise during active cancer treatment?

    Dr. Catherine Alfano: Being treated for cancer makes many patients feel like they have no control over their health and that causes them enormous anxiety. Patients are really looking for things that they can do to take the reins of control back over their health to improve their long-term health and well-being during treatment.

    I want to underscore the importance of the oncology team in helping patients improve their exercise. Research has shown that 50% of patients undergoing cancer treatment are not getting enough exercise. Patients want to receive guidance about exercise from their oncology team. And importantly, patients whose oncology clinicians discuss exercise with them are more likely to make these healthy behavior changes.

    So, it really underscores the importance of the oncology team in helping patients to access these important components of their health that they're asking for. The appropriate referral for exercise in patients undergoing treatment for cancer can really depend on several factors such as comorbidities, treatment toxicities, and the patient's pre-existing physical activity level. For example, many patients can safely perform unsupervised exercise, but others may need supervised cancer-specific exercise because they've got problems that they need to deal with clinically supervised exercise or to participate in a formal cancer rehabilitation program prior to undertaking exercise on their own.

    I want to highlight for everyone that there are national efforts that are focusing on building referral algorithms and clinical decision support tools to help point to the most safe, feasible, and effective intervention for a given patient.

    Brittany Harvey: Excellent. Well, thank you both so much for outlining the recommendations here and describing the nuance that the expert panel went through. It was certainly a large effort that you've helped lead. And so, I want to thank you so much for your work on these guidelines, and for your time today, Dr. Ligibel and Dr. Alfano.

    Dr. Jennifer Ligibel: Thanks for having us.

    Dr. Catherine Alfano: Thank you.

    Brittany Harvey: Thank you to all of our listeners for tuning in to the ASCO guidelines podcast series. To read the full guideline go to www.asco.org/supportive-care-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

    Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.


    Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline May 13, 2022
    Show notes

    An interview with Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, VA, Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, FL, and Dr. Vinai Gondi from Northwestern Medicine Cancer Center Warrenville and Proton Center in Warrenville, IL, authors on "Radiation Therapy for Brain Metastases: American Society of Clinical Oncology Guideline Endorsement of the American Society for Radiation Oncology Guideline." An ASCO endorsement panel endorsed the "Radiation Therapy for Brain Metastases: an ASTRO Clinical Practice Guideline," and the authors review the endorsement process and key points in this episode. Read the full guideline endorsement at www.asco.org/neurooncology-guidelines.

    TRANSCRIPT

    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts.

    My name is Brittany Harvey, and today I'm interviewing Dr. David Schiff, from the University of Virginia Medical Center in Charlottesville, Virginia, Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, Florida, and Dr. Vinai Gondi from Northwestern Medicine Cancer Center Warrenville and Proton Center in Warrenville, Illinois, authors on 'Radiation Therapy for Brain Metastases: American Society of Clinical Oncology Guideline Endorsement of the American Society for Radiation Oncology Guideline'.

    Thank you for being here, Dr. Schiff, Dr. Vogelbaum, and Dr. Gondi.

    Drs. Schiff, Vogelbaum, and Gondi: Our pleasure.

    Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guideline products and ensures that the ASCO conflict of interest policy is followed for each guideline product.

    The full conflict of interest information for this guideline endorsement panel is available online with the publication in the Journal of Clinical Oncology. Dr. Schiff, do you have any relevant disclosures that are directly related to this topic?

    Dr. David Schiff: No relevant disclosures, Brittany.

    Brittany Harvey: Thank you. And Dr. Vogelbaum, do you have any relevant disclosures that are related to this topic?

    Dr. Michael Vogelbaum: I have no relevant disclosures.

    Brittany Harvey: Thank you. And Dr. Gondi, do you have any relevant disclosures that are related to this topic?

    Dr. Vinai Gondi: Brittany, my only relevant disclosure is that I served as vice-chair of the guidelines that we're discussing today, but otherwise, no relevant disclosures.

    Brittany Harvey: Excellent! Thank you all. So, then starting us off, Dr. Schiff, what is the scope of this guideline endorsement? And how does it intersect with the recently published 'Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline'?

    Dr. David Schiff: Sure. A little bit of background, from the start of the joint ASCO and SNO guideline effort, we had the participation of radiation oncologists, in addition to neurosurgeons, medical oncologists, and neuro-oncologists.

    As we were getting underway, ASTRO reached out asking to participate formally as well. They had been planning to update their brain metastasis guidelines but were a year or two away from getting started. And they recognized it would be redundant for them to create comprehensive guidelines that covered chemotherapy, immunotherapy, and surgery as our guidelines were poised to do.

    By participating with ASCO and SNO, they were able to have their task force focus specifically on key questions related to radiation oncology practices. In particular, the ASTRO project went into considerable depth on issues of radiation and radiosurgery dose, fractionation schemes, and the risk of radiation complications.

    These were areas that our guidelines didn't address. Several members of the ASTRO task force including their chair, Paul Brown, and co-chair Dr. Gondi were members of our committee, and we added Dr. Brown as a co-chair to our committee when ASTRO came on board. The overlap between our two groups helped ensure that our recommendations were in harmony.

    Brittany Harvey: So, then, Dr. Vogelbaum, can you provide us with an overview of how the ASCO guideline endorsement process works?

    Dr. Michael Vogelbaum: Sure, Brittany. So, as Dr. Schiff mentioned, ASCO had convened a guidelines panel to develop the new 'Treatment for Brain Metastasis: ASCO-SNO-ASTRO Guideline'. And this was a multidisciplinary panel that he and I co-chaired and was anchored by a guideline specialist from ASCO, Hans Messersmith, and the process was that we had evaluated recent literature pertaining to the treatment of the brain metastases, and so, we had a very good understanding of what was supported by high-quality evidence and what was not there yet, as a group. So, when ASTRO came to ASCO and asked whether or not we would be interested in endorsing their guidelines, we were already prepared with all the evidence.

    And so, the same panel got together again, to evaluate the ASTRO guidelines. And we did this, again, in a very structured manner. We reviewed the guideline questions and recommendations, compared them to the evidence, and went through the same type of review and polling process that we had when we had developed our own original guidelines.

    In the end, we had a conversation with the ASTRO guidelines leadership about some of the points that we raised questions about, and we were able to reach an accommodation that allowed us to fully endorse the ASTRO guidelines.

    Brittany Harvey: Thank you, Dr. Vogelbaum for that overview of the endorsement process. So, then, Dr. Gondi, what are the key recommendations of the ASTRO guideline?

    Dr. Vinai Gondi: Thank you, Brittany. As Dr. Schiff and Dr. Vogelbaum outlined, ASTRO commissioned a list of key questions that they sought to address specifically to inform the radiotherapeutic management of brain metastases. And to address these questions, ASTRO not only convened a panel of expert radiation oncologists across the country but also engaged with the Agency for Healthcare Research and Quality (AHRQ) to create a comparative effectiveness evidence review, in addition to our own high-level evidence review to address these questions.

    The four key questions that were addressed in the ASTRO guidelines are:

    Number one: What are the indications for stereotactic radiosurgery alone for patients with intact brain metastases?

    Number two: What are the indications for observation, preoperative radiosurgery or post-operative radiosurgery, or whole-brain radiotherapy in patients with resected brain metastases?

    Number three: What are the indications for whole-brain radiotherapy for patients with intact brain metastases?

    Number four: What are the risks of symptomatic radionecrosis with whole-brain radiotherapy and/or stereotactic radiosurgery for patients with brain metastases?

    The recommendations that were made are based on a high-level review of a considerable amount of literature over the past several years that addressed these specific questions. I would encourage the listeners to this podcast to read through the guidelines to understand the specific nuances of each of those recommendations.

    Brittany Harvey: Excellent! Thank you for that overview. Then, in addition to what Dr. Gondi just said, Dr. Vogelbaum, were there any additional points of discussion raised by the ASCO endorsement panel?

    Dr. Michael Vogelbaum: Brittany, yes, there was an area of discussion where we needed to interact with the ASTRO guidelines leadership, as I mentioned earlier, and it really related to that key question one that Dr. Gondi described, which is what are the indications for SRS alone for patients with intact brain metastasis.

    The approach that had been strongly endorsed by ASCO was that there would be a multidisciplinary approach to decision making. And really the benefit of that, the value of that radiosurgery really comes in the form of the interaction between the radiation oncologist and the neurosurgeon.

    The way that the original proposal had been formulated, there was a size cut-off that was higher than we thought was appropriate for really endorsing that kind of conversation between the radiation oncologist and the neurosurgeon.

    And so really, we proposed that we bring that cut-off down further, there actually was another subpart to the guideline that had looked at a lower cut-off, but did not specifically call out that interaction between the neurosurgeon and the radiation oncologist. And we felt it would be more appropriate to insert that at that cut-off rather than the larger lesion cut-off.

    And after a conversation, there was agreement, that was really the only guideline or subpart of the guidelines where there was any real debate or discussion. For the rest of it, the comments that came up from the panel were easily addressed and it really just came down to this one modification. And fortunately, ASTRO agreed, and we were able to go ahead and complete the endorsement.

    Brittany Harvey: Great! It's great that this was able to be a complete endorsement of that guideline. So, then, Dr. Gondi, in your view, what is the importance of this guideline endorsement? And how will it affect ASCO members?

    Dr. Vinai Gondi: Thank you, Brittany. A number of responses to that. Number one is, as Dr. Vogelbaum, outlined the purpose of these guidelines was meant to be patient-centric and patient-focused, that we had patient champions who had navigated, who are part of the guideline development team, but also to be multidisciplinary. And so, the type of input and feedback we received from the ASCO team was super valued and valuable, as we were formulating these guidelines and Dr. Vogelbaum outlined a good example.

    Number two, it had been almost a decade since the last guidelines had come out from ASTRO related to brain metastases management. And much has happened in our field over the past several years that has been practice-changing. We have several novel and innovative radiotherapy technologies and techniques, such as the emergence of radiosurgery, the use of novel radioprotectants, such as hippocampal avoidance, and memantine, but also the emergence of innovative and novel neurosurgical interventions and CNS active systemic therapies.

    So, the modern management of brain metastases has really undergone quite a revolution over just the past few years, and it is important that these guidelines be updated to reflect those changes, but also to inform radiation oncologists on the contemporary management of brain metastases and in evidence-based care.

    So, we believe that these guidelines will significantly impact ASCO members. Certainly, those who are radiation oncologists, as brain metastases are some of the most common patients that radiation oncologists manage in the community and in academic centers, but also for other members of ASCO medical oncologists, surgeons to understand sort of the nuances of radiotherapy management that is evidence-based, so they can have a patient-centered, patient-focused, multidisciplinary discussion with their radiation oncologist as well.

    Brittany Harvey: Those are excellent points for clinicians on the management for brain metastases. So, then finally, Dr. Schiff, Dr. Gondi just mentioned how these guidelines are patient-centric. So, how will these guideline recommendations impact patients with brain metastases?

    Dr. David Schiff: Yeah, well, I think what I'm about to say is really going to echo what Dr. Gondi just said. You know, 20 years ago, patients diagnosed with brain metastases were typically immediately referred to a radiation oncologist, they almost always got whole-brain radiation therapy, the median survival was about four months, and many, if not most patients, died from their brain metastases.

    The situation has really changed recently. With the rapid advances in management from new therapies, and well-designed clinical trials in recent years, outcomes have markedly improved, it's probably less than a quarter of patients now who succumb to their intracranial disease. But at the same time, decision-making for patients has become much more complicated.

    Nowadays, medical oncologists may reach out initially to neurosurgeons for consideration of radiosurgery or surgical resection, or in some circumstances utilize systemic therapy as a first step.

    Conversely, a patient might see a neurosurgeon first, who may or may not be aware that there's appropriate immunotherapy or targeted agent that might make sense prior to going on to radiosurgery.

    It's obviously a challenge for sub-specialists to keep up with all the emerging clinical trial data and new drugs. Our two sets of guidelines provide a roadmap for physicians of different expertise to help determine what types of therapies or referral should be considered when brain metastases are found. The end result of all this is improved control of intracranial disease and improved quality of life for the patients.

    Brittany Harvey: Absolutely. Those are key points. It's excellent to see these guidelines, and the overarching 'Treatment for Brain Metastases: ASCO-ASTRO-SNO Guideline' be published. So, I want to thank you all for your time today, Dr. Schiff, Dr. Vogelbaum, and Dr. Gondi. Thank you for all of your work on these guidelines.

    Dr. Michael Vogelbaum: My pleasure.

    Dr. Vinai Gondi: Thank you for having us.

    Dr. David Schiff: Thank you, Brittany. It was great to participate in this important project.

    Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline endorsement go to www.asco.org/neurooncology-guidelines.

    You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

    Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.


    Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer Guideline Update Apr 19, 2022
    Show notes

    An interview with Dr. Fabrice André from Institute Gustave Roussy in Paris, France, and Dr. Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, NY, authors on "Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update." This updated guideline provides precise guidelines on previously endorsed genomic assays and recommendations on the use of new biomarkers to guide endocrine therapy and chemotherapy in patients with ER-positive HER2-negative tumors, and for those with HER2-positive or triple-negative breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines.

    TRANSCRIPT

    Brittany Harvey: Hello and welcome to the ASCO guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one asco.org/podcasts.

    My name is Brittany Harvey, and today I'm interviewing Dr. Fabrice André from Institut Gustave Roussy in Paris, France, and Dr. Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, NY, authors on "Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update." Thank you for being here Dr. André and Dr. Jhaveri.

    Dr. Fabrice André and Dr. Komal Jhaveri: Thank you.

    Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of guidelines and ensuring that the ASCO conflict of interest policies follow each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. André, do you have any relevant disclosures that are directly related to this guideline.

    Dr. Fabrice André: No.

    Brittany Harvey: Thank you. And Dr. Jhaveri, do you have any relevant disclosures that are related to this guideline topic?

    Dr. Komal Jhaveri: No.

    Brittany Harvey: Great, then let's talk about the content of this guideline update. So, Dr. Jhaveri, what prompted the update to the biomarkers for adjuvant endocrine therapy and chemotherapy in early-stage breast cancer, and what is the scope of this guideline update?

    Dr. Komal Jhaveri: So, since the biomarker guideline published in 2016, there were several new publications that came out between January 2016 and October 2021 that provided perspectives on the use of some of the genomic assays broadly, or specifically in women based on menopausal status, age or number of lymph nodes.

    Additionally, new biomarkers such as programmed cell death receptor ligand 1 or PD-L1, stromal TILs, circulating tumor DNA, or circulating tumor cells, or new applications, like extended endocrine therapy have also been developed.

    So, this updated guideline provides precise guidelines on previously endorsed genomic assays and also provides recommendations on the use of new biomarkers to guide endocrine therapy and chemotherapy in ER-positive HER2-negative, HER2-positive, and triple negative breast cancer.

    Brittany Harvey: Great. Thank you for setting the stage for this guideline. So, then Dr. André, I'd like to review the key recommendations of the guideline for our listeners. So, starting with, which biomarkers should be used to guide decisions on adjuvant endocrine and chemotherapy for patients with newly diagnosed ER-positive HER2-negative breast cancer?

    Dr. Fabrice André: Thank you. So, when we are focusing on a newly diagnosed patient with ER-positivity HER-2 negative in the context of the question about deciding on chemotherapy. First, the 21 gene recurrence score should be used in patients with node-negative and in patients with 1-3 node positive who are postmenopausal.

    In premenopausal, this test will be used only in patients with node-negative. The second test that is recommended is the MammaPrint 70-gene signature. And here the recommendation is to use this test if the patient is older than 50 and is node-negative or 1-3 node-positive.

    If the patient is 50 years or younger, the clinician should not use this test. Then also a recommendation is that the clinician could use the 12 gene risk score EndoPredict if the patient is postmenopausal and has breast cancer node negative or 1-3 positive-node.

    And finally, for the genomic test for the patient, the doctor could use PAM50. If the patient is postmenopausal and has breast cancer that is node-negative. Something new in this recommendation is the recommendation that the clinician could use Ki67. If the patient is postmenopausal and has stage I-II breast cancer with very specific recommendations on the cut off for positivity.

    Brittany Harvey: Great. Thank you for reviewing those recommendations, Dr. André, and highlighting the new Ki67. So, then, in your introduction, Dr. Jhaveri, you discuss the application of assays for extended endocrine therapy. So, which biomarkers should be used to guide decisions regarding extended endocrine therapy for patients with ER-positive HER2-negative breast cancer?

    Dr. Komal Jhaveri: Thank you. So, a quick word about extended endocrine therapy. I think extended adjuvant endocrine therapy, which is beyond five years of primary endocrine therapy, has certainly demonstrated improved outcomes, however, with modest absolute benefit and added toxicity and tolerability issues. Furthermore, while extended endocrine therapy is endorsed by clinical practice guidelines, clear guidance on individualized approaches to optimize patient selection for prolonged endocrine regimens, also remains limited. And this really underscores the need for prognostic and predictive information from genomic assays that can help guide this important clinical question we face.

    One such example that has now borne out has been the breast cancer index and really collected evidence from now five studies supports the prognostic and predictive utility of this assay, such that if a patient has node-negative or one to three positive nodes, and has been treated with five years of primary endocrine therapy, to guide decisions about extended endocrine therapy, the clinician may offer Breast Cancer Index with either tamoxifen or aromatase inhibitors or tamoxifen, followed by an aromatase inhibitor.

    Brittany Harvey: Great, thank you, Dr. Jhaveri. So, then, Dr. André, which biomarkers should be used to guide decisions on adjuvant therapy for early-stage HER2-positive breast cancer or triple-negative breast cancer?

    Dr. Fabrice André: Well, first, we have to be sure that we are good at defining HER2-positive breast cancer and triple-negative breast cancer. So, it's always good to remind colleagues to have quality control assessment in place for HER2, estrogen receptor, and progesterone receptor stainings.

    So far, when it's about predicting the benefit of adjuvant chemo or trastuzumab, there is no genomic test that is recommended in patients with HER2-positive or triple-negative breast cancer.

    Brittany Harvey: Great, thank you. So, then, Dr. Jhaveri, what recommendations did the expert panel make regarding emerging biomarkers?

    Dr. Komal Jhaveri: When we're talking about emerging biomarkers, we're referring to stromal TILs, we're referring to PD-L1, circulating tumor cells, and circulating tumor DNA. And while there is a lot of emerging data, currently, clinicians should not be utilizing these new biomarkers to guide decisions about adjuvant endocrine therapy or chemotherapy, as we do not have sufficient evidence to support their use.

    Brittany Harvey: Great and that's important for clinicians to know. So, then finally, Dr. André, in your view, how will these updated guideline recommendations impact both clinicians and patients?

    Dr. Fabrice André: So, we know Komal mentioned this at the beginning that now there is a very large amount of new publications, new data coming every day in the field of cancer. So, the only way for clinicians to deliver the best treatments for patients is to have the right guidelines with the right methodology, and ASCO is really putting in place a very rigorous methodology to deliver guidelines.

    And this is the best way to be sure that all patients will have access to the best decision by the doctor. So guidelines are also here to decrease the disparities in terms of the expert decision, and any patient in the world can have access to the best decision, thanks to guidelines delivered by ASCO and all the colleagues of the panel that worked very hard to deliver these guidelines.

    Brittany Harvey: Excellent! Well, thank you both so much, and the entire expert panel for your work to update these guidelines, and for taking the time to speak with me today, Dr. André and Dr. Jhaveri.

    Dr. Komal Jhaveri: Thank you.

    Dr. Fabrice André: Thank you, Brittany.

    Brittany Harvey: Thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines in interactive resources in the free ASCO guidelines app available in iTunes or Google Play Store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO the mention of any product or service organization activity or therapy should not be construed as an ASCO endorsement.


    Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-risk, Early-stage Triple Negative Breast Cancer Rapid Recommendation Update Apr 13, 2022
    Show notes

    An interview with Dr. Lisa Carey from the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, NC, panel member on "Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-risk, Early-stage Triple Negative Breast Cancer: ASCO Guideline Rapid Recommendation Update." Dr. Carey discusses the updated recommendation on the use of pembrolizumab for patients with T1cN1-2 or T2-4N0 (stage II or III), early-stage triple negative breast cancer. For more information, visit, www.asco.org/breast-cancer-guidelines.

    TRANSCRIPT

    Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one at asco.org/podcasts.

    My name is Brittany Harvey, and today I'm interviewing Dr. Lisa Carey from the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, expert panel member on Use of Immune Checkpoint Inhibitor Pembrolizumab in the Treatment of High-risk Early-stage Triple-negative Breast Cancer: ASCO Guideline Rapid Recommendation Update. Thank you for being here, Dr. Carey.

    Dr. Lisa Carey: It's a pleasure to be here, Brittany. Thank you!

    Brittany Harvey: Great! First, I like to note that ASCO takes great care in the development of its guidelines and ensures that the ASCO conflict of interest policy is followed for each guideline.

    The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Carey, do you have any relevant disclosures that are directly related to this guideline topic?

    Dr. Lisa Carey: I do not.

    Brittany Harvey: Thank you. Then what prompted this rapid update to the Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline, which was last published in 2021?

    Dr. Lisa Carey: You know, what prompted it where there were a number of changes that had come out, particularly things like the use of immune checkpoint inhibitors, and the adoption of the neoadjuvant strategy that really made us feel that these were overdue for practice guidelines. And in particular, there were some very important changes that came out early this year, particularly with the pembrolizumab use.

    Dr. Brittany Harvey: Great, so, based on these changes in the pembrolizumab use, what is the updated recommendation from the guideline panel?

    Dr. Lisa Carey: The recommendation actually is for patients who fulfilled the KEYNOTE-522 trial criteria. KEYNOTE-522 was a seminal trial in early triple-negative breast cancer, meaning, treatment-naive of the use of pembrolizumab incorporated into a chemotherapy-based regimen given neoadjuvantly, and then with the continuation of the immune checkpoint inhibitor pembrolizumab adjuvantly.

    This was important because we had been using, for a couple of years now, immune checkpoint inhibitors in PD-L1 positive or immune-activated triple-negative breast cancers in the metastatic setting. But we had not had evidence of improved survival or outcomes in early triple-negative breast cancer, so that's where KEYNOTE-522 comes in. This was a trial in which patients with early untreated triple-negative breast cancer, who fulfilled at least greater than T1N0, - and I want to make that pretty clear, this is a pretty broad net for early triple-negative breast cancer; the vast majority of triple negatives will be eligible for this treatment based on the population that was studied - and they receive four chemotherapy drugs, so, a taxane plus platinum, followed by an anthracycline-based regimen, either with or without pembrolizumab throughout the entire neoadjuvant course. They then went to surgery, and then they went on to receive adjuvant for another nine cycles, adjuvant pembrolizumab.

    The trial had already reported an improvement in pathologic complete response with the addition of the immune checkpoint inhibitor, which has also been seen with other immune checkpoint inhibitors. But what was reported a few months ago, and then published early this year, was the impact on event-free survival. So, there was a statistically significant improvement in event-free survival with the addition of pembrolizumab, which, at that point, it's a highly clinically meaningful endpoint, there are now two highly clinically meaningful endpoints. Both of these were the primary endpoints of this study. And so, it has rapidly been adopted on that basis for use and we felt because of that it needed to be addressed in a rapid update for helping clinicians interpret the data and use them effectively.

    Brittany Harvey: Understood, and I appreciate your work and the panel's work to rapidly interpret this data. So then, what should clinicians know as they implement this recommendation for the use of pembrolizumab?

    Dr. Lisa Carey: I think the key elements are unlike the metastatic setting, there's really no role for PD-L1 testing in the early triple-negative setting because the pembrolizumab seemed to improve outcomes regardless of PD-L1 status, which is a big difference from what's true in the metastatic setting where all of these immune checkpoint inhibitors seem to only benefit patients that are PD-L1 positive. So, it's kind of regardless of PD-L1 status.

    It's also true that in the KEYNOTE-522 study when they did do PD-L1 testing, most early triple negatives are PD-L1 positive. There really wasn't a subset of patients in the trial. And again, this is T2 or greater in tumor size or node-positive, who didn't seem to benefit from it.

    So, it's a pretty broad recommendation. The 'however' is that, as we all know at this point, when you add immune-directed therapies, you have a different set of toxicities you have to be aware of, specifically what they call immune-related adverse events or irAEs, which are, of course, essentially autoimmune.

    The thing that you have to remember is these can be permanent. These are frequently glandular disorders. Typically things like thyroid disease, which can be handled with replacement, but you can sometimes have colitis, myositis of different kinds, pneumonitis, and things like that. And some of these can be permanent.

    So, they have to be monitored very carefully. And ASCO has a guideline for managing irAEs and patients treated with immune checkpoint inhibitors - because again, we use these in lots of tumor types - that gives a lot of detailed practice recommendations, that clinicians should really consult frequently, not just in triple-negative, but in other disease types that we use these drugs.

    Brittany Harvey: Great. Thanks for explaining that aspect of the guideline. So then, you just mentioned that this recommendation is broadly applicable to many patients with early-stage triple-negative breast cancer. So, how will these guideline recommendations impact patients with early-stage triple-negative breast cancer?

    Dr. Lisa Carey: Well, it means that it's a totally new game. So, as you are evaluating a patient, first off, virtually all of these are treated neoadjuvantly now, except for the T1N0s, and pembrolizumab and the addition of pembrolizumab should be considered in all of them.

    Again, if they have, particularly organ-threatening autoimmune disorders themselves, they are a poor choice for these drugs, but otherwise, it should at least be considered. It's also true that there's been for many years a debate about the optimal chemotherapy to give in triple-negative breast cancer in the backbone that was used to which pembro was added had four drugs in it. And I think for that reason, that is considered the standard of care now.

    I do think one of the challenges for us moving forward is to decide if we need all of those drugs or not. I think a challenge for us also is to figure out who actually benefits from, again, these are five drugs, you know, a lot of therapy, a fair amount of toxicity. And so, I think that's a challenge going forward.

    Brittany Harvey: Thank you. And then finally, you just mentioned a couple of upcoming challenges, including the debate about the optimal chemotherapy regimen. But what are the outstanding questions regarding neoadjuvant therapy for patients with breast cancer?

    Dr. Lisa Carey: I think the outstanding questions regarding neoadjuvant therapy are one thing. I think neoadjuvant therapy, there isn't a lot of outstanding questions that are medically related other than what's the right backbone and things like that, because I think the neoadjuvant paradigm, if you're just purely talking about whether you're giving drugs before or after surgery, the drugs themselves tend to be the same because the key endpoint for the medical oncologist and for the patient, of course, is their outcome from a relapse standpoint.

    But it's also true that the neoadjuvant approach allows tailoring of the medical therapy. Like, in the past before we had immune checkpoint inhibitors, patients who received chemotherapy and had residual disease would get additional chemotherapy.

    That wasn't allowed in the KEYNOTE study. So, I think many people, because patients with residual disease in KEYNOTE, still had pretty poor outcomes are incorporating additional chemotherapy, specifically adjuvant capecitabine with the pembrolizumab, but there's no data for that.

    So, I think that's a challenge that we do have to address. I think the other challenge is simply surgical management: whether we can use these improved pathologic response and clinical response outcomes to minimize some of the local therapies, in addition to tailoring the medical therapies.

    Brittany Harvey: Great! Well, we look forward to maybe tackling some of these challenges when we have more data in upcoming guidelines. I want to thank you so much for your time to rapidly update these guideline recommendations and for your time speaking with me today, Dr. Carey.

    Dr. Lisa Carey: It's my pleasure. Thank you so much, Brittany.

    Brittany Harvey: Thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

    Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product service organization activity or therapy should not be construed as an ASCO endorsement.


    Management and Care of Patients with Invasive Cervical Cancer: Resource-Stratified Guideline Rapid Recommendation Update Mar 07, 2022
    Show notes

    An interview with Dr. Linus Chuang from Danbury Hospital and Norwalk Hospital, Nuvance Health in Connecticut and New York, co-chair on "Management and Care of Patients with Invasive Cervical Cancer: ASCO Resource-Stratified Guideline Rapid Recommendation Update." Dr. Chuang discusses the updated recommendation on the use of pembrolizumab in patients with persistent, recurrent, or metastatic cervical carcinoma, based on the results from the KEYNOTE-826 study. For more information, visit, www.asco.org/resource-stratified-guidelines.

    Transcript

    BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts.

    My name is Brittany Harvey, and today I'm interviewing Dr. Linus Chuang from Danbury Hospital in Norwalk Hospital, Nuvance Health, in Connecticut and New York, Co-Chair on "Management and Care of Patients with Invasive Cervical Cancer-- ASCO Resource-Stratified Guideline Rapid Recommendation Update." Thank you for being here, Dr. Chuang.

    LINUS CHUANG: Thank you for having me.

    BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline is available online with a publication in the Journal of Clinical Oncology Global Oncology. Dr. Chuang, do you have any relevant disclosures that are directly related to this guideline topic?

    LINUS CHUANG: No, Brittany.

    BRITTANY HARVEY: Thank you. Then talking about the content of this publication, so what prompted this rapid update to the "Management and Care of Patients with Invasive Cervical Cancer-- ASCO Resource-Stratified Clinical Practice Guideline," last published in 2016?

    LINUS CHUANG: ASCO Rapid Recommendations Updates highlight revisions to ASCO guideline recommendations on "Management and Care of Women with Invasive Cervical Cancer, the ASCO Resource-Stratified Clinical Practice Guideline" that was published in September of 2016. We revised the guidelines to reflect new and practice-changing data on the use of pembrolizumab combination therapy in patients with metastatic, recurrent, or persistent cervical cancer in enhanced and maximal settings.

    BRITTANY HARVEY: Great. Then based off this new data for the pembrolizumab combination therapy, what are the updated recommendations from the guideline panel?

    LINUS CHUANG: Based on this recently published report about the KEYNOTE-826 study, the checkpoint inhibitor pembrolizumab alongside standard chemotherapy with or without bevacizumab as first-line therapy significantly improved the overall and progression-free survival in patients with persistent, recurrent, or metastatic PD-L1 expressing cervical cancer.

    BRITTANY HARVEY: Great. Thank you for providing that recommendation. So what should clinicians know as they implement these recommendations, and for which settings do these recommendations apply?

    LINUS CHUANG: This trial included 617 patients, pembrolizumab 200 milligrams delivered intravenously every three weeks in combination with standard chemotherapy and with or without bevacizumab for up to 35 cycles. It's worth emphasizing based on the following study results the median progression-free survival was 2.2 months longer in the pembrolizumab group that have a PD-L1 combined positive score of 1 or more. And the progression-free survival at 12 months was also longer by 20% in the pembrolizumab group when compared to the placebo group. The overall survival rate at 12 and 24 months were higher in the pembrolizumab group-- 75% and 53% respectively-- compared with the placebo cohort-- 63% and 41% respectively.

    According to the study, the most common adverse reactions, which occur in more than one in five patients in the pembrolizumab group, are anemia, neutropenia, alopecia, and peripheral neuropathy. Based on this data our rapid communication recommended this regimen be used in the enhanced and maximal settings where the pembrolizumab is available.

    BRITTANY HARVEY: Great. Thank you for reviewing that data in the context of this recommendation. So how will these guideline recommendations impact patients?

    LINUS CHUANG: So pembrolizumab with the standard chemotherapy with or without bevacizumab demonstrated improvement in the progression-free and overall survival much longer than those without the pembrolizumab group. And this has emerged as a front-line therapy for the group of patients that have persistent, recurrent, or metastatic cervical cancer with PD-L1 expression cervical cancer.

    BRITTANY HARVEY: OK, thank you. And then finally, what emerging evidence is the panel anticipating regarding treatment of invasive cervical cancer?

    LINUS CHUANG: This is an exciting time. Exploration of other PD-1 and PD-L1 inhibitors, monotherapy, or as part of combination therapy for cervical cancer will expand the management of patients with recurrent or metastatic cervical cancer that progressed after platinum-based chemotherapy. It is also important to explore the ability of pembrolizumab with chemoradiation with or without concurrent and maintenance pembrolizumab to improve outcomes for patients with high-risk locally advanced cervical cancer.

    BRITTANY HARVEY: Great. That's very exciting to see that evidence coming to fruition. So I want to thank you so much for your work to rapidly update this guideline and for your time tonight, Dr. Chuang.

    LINUS CHUANG: Thank you for having me today.

    BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/resource stratified guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

    SPEAKER 3: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.


    Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update Feb 24, 2022
    Show notes

    An interview with Dr. Andrea Eisen from Sunnybrook Odette Cancer Centre and Ontario Health in Toronto, Ontario, co-chair on "Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update." This guideline updates recommendations for which patients with primary breast cancer should be treated with bone-modifying agents, and which bisphosphonates are optimal. Read the full guideline at www.asco.org/breast-cancer-guidelines.

    TRANSCRIPT

    [MUSIC PLAYING]

    BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at ASCO.org/podcasts.

    My name is Brittany Harvey, and today I'm interviewing Dr. Andrea Eisen from Sunnybrook Odette Cancer Center and Ontario Health in Toronto, Ontario, lead author on "Use of Adjuvant Bisphosphonates and other Bone-Modifying Agents in Breast Cancer," American Society of Clinical Oncology and Ontario Health Cancer Care Ontario Guideline Update. Thank you for being here, Dr. Eisen.

    ANDREA EISEN: Thanks very much for the opportunity.

    BRITTANY HARVEY: And I'd like to note that ASCO takes great care of the development of its guidelines and ensuring that the ASCO conflict-of-interest policy is followed for each guideline. The full conflict-of-interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Eisen, do you have any relevant disclosures that are directly related to this guideline topic?

    ANDREA EISEN: I have no disclosures.

    BRITTANY HARVEY: Thank you. Then let's talk about the content of this guideline. So what prompted an update to this guideline published in 2017, and what is the scope of this update?

    ANDREA EISEN: So ASCO has a guideline update process which triggers updates and reviews when new data are available. And for this particular guideline, an update was prompted by publication of three randomized trials. And during the update process, a fourth trial was published that was relevant for the guidance document.

    BRITTANY HARVEY: Great. That's great background. So then next, I'd like to review the key recommendations of this guideline for each clinical question, starting with, which patients with primary breast cancer should be treated with bone-modifying agents?

    ANDREA EISEN: The first recommendation for this guideline is that adjuvant bisphosphonate therapy should be discussed with all postmenopausal breast cancer patients, regardless of their hormone receptor status, or HER2 status, who are candidates to receive adjuvant systemic therapy.

    BRITTANY HARVEY: Great. And then what is recommended for which bisphosphonates should be used for breast cancer adjuvant therapy, and what doses, duration of administration, time to initial treatment, and routes are optimal?

    ANDREA EISEN: For this question, there were a number of different regimens available for review and inclusion in the guideline, because the studies used several different treatment protocols. However, the guideline recommends that adjuvant bisphosphonates should be started early, and ideally within three months of the definitive surgery or within two months of completion of adjuvant chemotherapy. The options for treatment include oral clodronate, oral ibandronate, or several different dosing regimens of zoledronic acid.

    BRITTANY HARVEY: Great. So then you've just mentioned three different bisphosphonates. So what is the role of the bone-modifying agent denosumab as an adjuvant therapy for primary breast cancer?

    ANDREA EISEN: This was a difficult, and perhaps the most contentious area that the committee considered, because there are two very important clinical trials that were reviewed. The first, the ABCSG trial, and the second was the more recently published D-CARE study. The guideline committee does not recommend the use of adjuvant denosumab for the prevention of breast cancer recurrence in early stage breast cancer patients.

    BRITTANY HARVEY: That's helpful for clinicians to know, both which are recommended and which aren't recommended at this time. So then finally, Dr. Eisen, in your view, what is the importance of this guideline update, and how does it impact both clinicians and patients with cancer?

    ANDREA EISEN: There are at least two issues that make this guideline particularly timely and important. First, there's new clinical trial guidance available, in particular with respect to scheduling and dosing of bisphosphonates and route of administration. These data also highlight the benefits of bisphosphonates.

    The second is that the new evidence confirms our previous recommendation that denosumab is not recommended as adjuvant treatment in early stage breast cancer patients. During the development of this update, it became apparent that the uptake of adjuvant bisphosphonate usage in breast cancer patients is probably suboptimal. And there is a number of reasons for this across different jurisdictions.

    Some reasons include variable access to different formulations of the bisphosphonates. For example, oral clodronate, which is well studied, is not available in the United States. The second issue that was highlighted was variable access for patients with respect to insurance coverage. And we also identified that even in jurisdictions where funding is fully provided for adjuvant bisphosphonates, uptake might be suboptimal.

    So we hope that publishing this guideline and reviewing the evidence and highlighting the potential benefits in terms of reduction in recurrence and improvement in survival will result in more utilization of the bisphosphonates. We recognize that there are potential toxicities associated with the treatment and that the benefits versus risks have to be weighed carefully. The guideline committee recommended the utilization of an online risk assessment tool to help in those discussions with patients and to determine which patients have sufficient risk to justify using bisphosphonates.

    BRITTANY HARVEY: Great. Those access issues are important to highlight. And I appreciate all of the work that you've done on this guideline update and also for taking the time to speak with me today, Dr. Eisen.

    ANDREA EISEN: Thanks very much.

    BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.ASCO.org/breast cancer guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in iTunes or the Google Play store. If you have enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

    ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.


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