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Management of Salivary Gland Malignancy Guideline Apr 26, 2021

Show notes

An interview with Jessica Geiger, MD, from Cleveland Clinic and Patrick Ha, MD, from the University of California, San Francisco, co-chairs on "Management of Salivary Gland Malignancy: ASCO Guideline." This guideline provides recommendations for preoperative evaluation, surgical procedures, radiotherapy techniques, the role of systemic therapy, and follow-up evaluations for patients with salivary gland malignancies. Read the full guideline at www.asco.org/head-neck-cancer-guidelines. TRANSCRIPT SPEAKER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Jessica Geiger from Cleveland Clinic and Dr. Patrick Ha from the University of California San Francisco, co-chairs of management of salivary gland malignancy ASCO guideline. Thank you for being here, Dr. Geiger and Dr. Ha. DR. PATRICK HA: Thank you, Brittany. DR. JESSICA GEIGER: 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. Geiger, do you have any relevant disclosures that are directly related to this guideline? DR. JESSICA GEIGER: No, I don't. BRITTANY HARVEY: And Dr. Ha, do you have any relevant disclosures that are related to this guideline? DR. PATRICK HA: No, I do not. BRITTANY HARVEY: Thank you both. Then let's talk about some of the content of this guideline. So first, Dr. Geiger, can you give us a general overview of the purpose and the scope of this evidence-based guideline on the management of salivary gland malignancy? DR. JESSICA GEIGER: Sure. So salivary gland cancers-- they're relatively rare, and they encompass a wide variety of both histologies, but also biologic behaviors of cancers. This is a very multidisciplinary tumor, so surgeons, radiation oncologists, pathologists, medical oncologists-- they all play an integral role in treating these patients. And the purpose of this guideline was to bring all of these disciplines together and to develop an as strong as possible, evidence-based way of approaching the diagnosis of such cancers and then approaching it from all modalities of therapy-- surgical, radiotherapy, systemic therapy-- in a very evidence-based and organized fashion. BRITTANY HARVEY: Great, then as you just mentioned, this is a multidisciplinary guideline, and it covers six different subtopics on the management of salivary gland malignancy-- preoperative evaluation, surgical management, radiotherapy, systemic therapy, follow up, and treatment options for recurrent and metastatic disease. I'd like to go through and review the key recommendations from each of those sections for our listeners. So first, Dr. Ha, what is the guideline recommend regarding preoperative evaluation for patients with salivary gland malignancy? DR. PATRICK HA: Great, so I'd first like to start off by saying that we were focusing on salivary gland malignancy. So again, these are tumors where we may not know the diagnosis, but we're suspicious of this being cancer as opposed to a benign tumor. So along those lines, there are many different imaging recommendations-- first off, that some sort of imaging would be helpful if there's a suspicion of cancer, and then drilling down a little bit more specifically if there is concern about bone involvement. And then CT scan was recommended if it was more of a concern about the soft tissue or perineural invasion or skull-based invasion, then MRI was suggested. And we did spend some time focusing on the strength of and the importance of tissue biopsies, either with fine needle aspiration biopsy or core needle biopsy as a real helpful tool to help clinicians determine what sort of procedures and care this patient might need. Additionally, with the onset of more understanding of the pathology in the markers, it was felt that using these biopsies-- these FNAs or core biopsies-- to perform either molecular or immunohistochemical studies could further help clarify what the diagnosis would be and thus lead to sort of more specific and defined treatment subsequently. BRITTANY HARVEY: And then following those evaluation and imaging and biopsy recommendations, what are the key surgical recommendations? DR. PATRICK HA: Yeah, so again this is probably known to most people-- that when it is considered resectable, the surgery is really the mainstay upfront management option for these patients. We spent some time looking at the different types of surgeries and felt that it was a bit up to the discretion of the surgeon, but it depends on the location as to what type of surgery exactly needs to be done. But the idea is obviously we would want a complete resection of it and margins where possible. And then we address the nodes and the ability for these cancers to sometimes spread regionally. And basically, if these are high risk or high grade cancers, specifically if there are things like the grade of the tumor itself-- the type-- and then whether there were other concerning features about it, than a neck dissection electively would be offered. If there were N positive disease, then the neck dissection definitely should be performed. And then there was discussion as well about the facial nerve and how to manage that, wherein the evidence mostly reported trying to preserve the facial nerve whenever possible. And then we did talk a little bit about the possibility of palliative resection, which can occur sometimes in the presence of distant metastatic disease upon presentation. And it was felt again that there is a palliative component to surgery if the metastatic disease didn't seem to be rapidly progressive or imminently lethal. So these are all the difficult decisions that we discussed regarding surgery. BRITTANY HARVEY: OK, thank you. Then Dr. Geiger, how does this guideline address radiotherapy for patients with salivary gland malignancy? DR. JESSICA GEIGER: Well, as Dr. Ha mentioned, this is primarily a surgical disease. So most of the recommendations regarding radiotherapy involve the post-operative setting. But if you look at the guideline, we have actually laid out 10 recommendations regarding radiation, and they're dependent on various factors with each cancer, so the histology of the disease, other tumor pathologic factors, such as T-stage, vascular, lymphatic invasion, margin status, perineural invasion-- all of that goes into the recommendation here. There's also considerations for what nodal basins to cover, based on where the tumor is, and even the type of radiation, and, of course, the timing of radiation. All of that is important to be considered, and all of those specific features are mentioned within the recommendations. BRITTANY HARVEY: Great. And then in addition to those radiotherapy recommendations, what's the role of systemic therapy for patients with salivary gland malignancy? DR. JESSICA GEIGER: Well, unlike the radiation section, where I said we have 10 specific recommendations, we're limited with the evidence for the use of systemic therapy in the curative setting of these diseases. So one point that I will make is, again, we're very limited based on evidence, and this is what is driving such a guideline-- is evidence, evidence, evidence. And we just don't have it. There are several large studies that are ongoing, but until those results flesh out, we were limited. And so our recommendations are based on the lack thereof, and often are considered low quality or moderate strength of recommendation at best, based on our expert panel. Basically, outside of a clinical trial, we're not recommending the addition of radiosensitizing chemotherapy with post-op radiotherapy. Again, that can be contentious, especially in the clinical realm, where there's a wide variety of biologic behavior. So some of the more aggressive diseases, we know that oncologists are advocating for the use of chemotherapy. But again, the evidence is not there yet, and so we weren't able to make that informative within this guideline. And then we also addressed tumors that are expressing different markers, like androgen receptor, HER2, and make a recommendation for the use of targeted therapy, again noting a lack of evidence for it outside of a clinical trial currently. BRITTANY HARVEY: OK, thank you for explaining the reasoning and the evidence behind those particular recommendations. So then for patients who have then completed treatment for salivary gland malignancy, Dr. Ha, what are the timelines and recommendations for follow up for these patients? DR. PATRICK HA: Well, so again, this is where the data are really not strong. And so you'll notice that pretty much all of these recommendations were informal in consensus. But similar to the NCCN guidelines for general cancer follow up was believed by the panel that early follow up more frequently and just sort of spaced out over time was important. And then there was an emphasis on some form of imaging often, whether that be CT or MRI, it's sort of up to the practitioner. And then perhaps for a couple of years after treatment, that might be important. It was also felt that, as everyone probably knows, that one of the areas where this may spread to distantly is in the lung. So getting some sort of chest imaging between years 2 and 5 would be important as well, just in case one can detect an asymptomatic yet potentially treatable metastasis. So again, a lot of informal consensus. The idea is that we feel it's important to continue to follow these patients to look for signs of recurrence, whether that's with imaging or physical exam. We thought that either would be an option. BRITTANY HARVEY: Definitely. And the last section of recommendations for this guideline is on recurrent or metastatic salivary gland malignancies. So what are those treatment options, Dr. Geiger? DR. JESSICA GEIGER: Well like before, when we're talking about systemic therapy, again, informal consensus is sort of driving the majority of these recommendations, again highlighting lack of strong evidence. That said, there are several different clinical situations that we address within these recommendations. So whether a patient presents with diffusely metastatic disease with a large tumor burden or oligometastatic disease, where maybe just one or two local or regional areas have recurred. And so in that latter case, you could discuss with the patient is it worthwhile to do some locally ablative therapy, such as SBRT, or possibly a resection versus, for more widely metastatic disease, starting systemic therapy. Now, there's also a recommendation specifically for the histology adenoid cystic carcinoma. And that is based on studies that have been done with tyrosine kinase inhibitors. And so there's some evidence for that outside of cytotoxic chemotherapy. And then we also make a mention, which is very important, again on checkpoint inhibitors, but also on some of the targeted therapies-- doing next generation sequencing, looking for molecular markers that drive the progression of these diseases, and then in subsequent targeted therapies for this. So we really try to encompass any and all particular situations that an oncologist may encounter with these diseases and offer some guidelines and recommendations regarding the appropriate management. BRITTANY HARVEY: Great. Thank you both for reviewing those key points of the recommendations. This guideline goes through a lot of content, and so it's interesting to hear more about what kind of those details are for each section. So Dr. Ha, in your view, what is the importance of this guideline, and how will it impact clinicians? DR. PATRICK HA: Well, I think that we realized we had a lot to cover in just a short amount of time. And I think that we felt that while the data may not be as strong with-- full of randomized clinical trials as perhaps other disease subgroups, we felt it was important to organize what the current state of the data are, because these are rare cancers, and there are some nuances between some of the histologies even that it may be difficult to keep up to date all the time. So organizing it into one document where it we have clearly delineated what areas we feel are common practice amongst experts and what areas actually do have some studies and perhaps some deeper level of understanding and depth of studies would be important, so that clinicians understood where it was that they have to be a little more creative and areas where they felt like hey, we feel like this is important to do. So I think that that would be useful for clinicians. And I think also it provides a framework for future studies, meaning that we hope that whenever these get updated and 5 or 10 years that there will be more studies. But it also does, I think, help for those of us who are in the field to organize where those gaps are so you can look at the guidelines and really understand OK, these are the areas that we need better understanding of how to treat patients. BRITTANY HARVEY: Definitely. It's helpful to understand both where there is evidence and where there is no evidence and where informal consensus takes rule. So then finally, Dr. Geiger, how will these guideline recommendations affect patients? DR. JESSICA GEIGER: Well, when it comes to cancer treatment, there is a lot of fear in the unknown. And I feel that patients are always asking am I doing the right things? Am I looking to make sure that I'm getting the best of care? And I think with any guideline-- this one included-- patients can rest assured that they don't have to make the trip and travel to a large academic center necessarily-- that they can feel comfortable knowing that their providers are following the data and following such guidelines that have been brought forth in one single document. Even though the patients aren't going to necessarily have this document at hand, they can have confidence within their oncology team. And then I think they'll also benefit from, as Dr. Ha was saying, as medical professionals being able to identify gaps and bring forth clinical trials. That's the only way that we're going to be able to move this field forward, particularly in such a rare disease that many histologies as salivary gland malignancies. And so while being treated in a regional oncology office or a community oncology office, maybe their provider will then recommend clinical trials that are open and have that additional opportunity for patients, if they so desire. So knowing that they're getting great standard of care based on evidence, but then also the opportunity to create new evidence for us to better treat patients in the future. BRITTANY HARVEY: Definitely. Well, I want to thank you both so much for your work on developing these evidence-based guidelines and for taking the time to speak with me today on the podcast, Dr. Geiger and Dr. Ha. DR. JESSICA GEIGER: Thanks. DR. PATRICK HA: Thank y…

Full show notes at the publisher

Management of Dyspnea in Advanced Cancer Guideline Feb 22, 2021

Show notes

An interview with Dr. David Hui from MD Anderson Cancer Center and Dr. Margaret L. Campbell from Wayne State University, co-chairs on "Management of Dyspnea in Advanced Cancer: ASCO Guideline." This guideline outlines a hierarchical approach to dyspnea management, beginning with identifying and managing potentially reversible causes, followed by the use of non-pharmacologic interventions, and then pharmacologic interventions. Read the full guideline at www.asco.org/supportive-care-guidelines

TRANSCRIPT

SPEAKER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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 podcast.asco.org.

My name is Brittany Harvey, and today I'm interviewing Dr. David Hui from MD Anderson Cancer Center in Houston, Texas, and Dr. Margaret Campbell from Wayne State University in Detroit, Michigan, co-chairs on "Management of Dyspnea in Advanced Cancer: ASCO Guideline." Thank you for being here, Dr. Hui and Dr. Campbell.

DR. DAVID HUI: Thank you. It's wonderful to be here.

DR. MARGARET CAMPBELL: Yeah, it's my pleasure.

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

DR. DAVID HUI: I have no relevant disclosures.

BRITTANY HARVEY: Thank you. And Dr. Campbell, do you have any relevant disclosures that are related to this guideline topic?

DR. MARGARET CAMPBELL: No, I do not have any relevant disclosures.

BRITTANY HARVEY: Thank you. Then let's get into some of the guideline content. So first, Dr. Hui, can you give us a general overview of the purpose of this clinical practice guideline?

DR. DAVID HUI: Yeah. This clinical practice guideline is on dyspnea in patients with advanced cancer. And this symptom of shortness of breath, or dyspnea, is very common in our patients and extremely distressing. And the evidence base is rapidly evolving, so the purpose of this guideline is then to summarize the up-to-date information and provide some recommendations for clinical practice to help alleviate this very challenging symptom.

BRITTANY HARVEY: Great. Then let's review some of those key recommendations of this guideline. So Dr. Campbell, what is recommended for screening and assessment of dyspnea in patients with advanced cancer?

DR. MARGARET CAMPBELL: Well, as David mentioned, this is a highly prevalent symptom. But we know that in clinical practice, sometimes patients won't disclose their symptom unless they're asked. And it gives us an opportunity to be certain that we don't overlook the symptom, particularly when it's in the early stages, mild or moderate stages, where we can intervene rapidly.

So in order to treat a symptom, we have to know that the symptom exists. So in the guideline, we recommend at every clinical encounter that there be an assessment for dyspnea. So every clinical encounter could be every time the patient presents in the outpatient clinic, or it could be every day if the patient is an inpatient. Every day on rounds, or every time vital signs are obtained, there would be an assessment of the patient's dyspnea.

BRITTANY HARVEY: Great. Then, reading through this guideline, it takes a hierarchical approach to the management of dyspnea, addressing first potentially reversible causes, then the use of non-pharmacologic interventions, and finally pharmacologic interventions. So first, what does the guideline state regarding addressing those potentially reversible causes of dyspnea?

DR. DAVID HUI: Yeah, well, this is a very important aspect that you highlighted is that we really want clinicians to remember that it's not just about treating this symptom. It's ideally identifying what are the causes of shortness of breath that we could reverse. And in many patients, there may be multiple factors contributing to the shortness of breath.

Some patients may have some effusion, perifusion contributing to it. They may also have underlying emphysema. And other times they may have some complications, such as blood clots. And so it's important to kind of identify the issues that may be at stake. And some of them are very treatable, and patients may have significant improvement in their shortness of breath right away.

So I think it's a combination of identifying the complications and comorbidities in those patients. And of course that along with treating the cancer if the cancer is the cause of the dyspnea as well.

BRITTANY HARVEY: Great. Then so after addressing those potentially reversible causes, Dr. Campbell, what are the recommended non-pharmacologic interventions?

DR. MARGARET CAMPBELL: Well, in the case of a patient whose dyspnea is not severe but is a difficult to tolerate symptom, we propose that the clinician begin with a hierarchical approach from the easiest, simplest interventions that are non-pharmacologic that may actually help improve the symptom experience. So that might be as simple as changing the patient's position.

And depending on where their cancer is located, they may find that they are more comfortable sitting up straight propped with pillows, for example. In addition, circulating air around the face has a fairly strong evidence base. And that can be accomplished, weather permitting, by putting the patient's chair near an open window. Or it can be accomplished with a small handheld fan blowing on the face.

For some patients whose blood oxygen levels are low, then the application of supplemental oxygen may be helpful to correct the low blood oxygen. Those are the major interventions that we would suggest, but there could be others. If the patient is still ambulatory, then perhaps a walking aid, avoiding stairs. And some of that comes back to our comprehensive assessment. If we could determine what triggers the patient's shortness of breath, then perhaps we can suggest interventions to minimize that, like pacing activity.

So similarly, if the patient's in the hospital but has dyspnea, we would want to pace their clinical activity. We wouldn't want them to have their bed, bath, their breakfast, their linen change, their physical therapy all in the same short period of time. We would want to see those interventions staggered through the day.

BRITTANY HARVEY: Definitely. That makes a lot of sense. So then, Dr. Hui, what pharmacologic interventions are recommended for patients with advanced cancer and dyspnea?

DR. DAVID HUI: Yeah, and so building on Dr. Campbell's discussion of the non-pharmacologic interventions, sometimes patients will continue to have quite a bit of shortness of breath. Or it's a very acute or severe presentation, such as in the hospital setting, then we do recommend some pharmacologic interventions.

So the front line measure for that would be systemic opioids. And I recognize that, nowadays, opioids, there's still a lot of stigma around the use of it and concerns. But it is after careful review by the committee and based on the existing evidence that we do recommend this as the main pharmacologic agent. For patients, of course, the use of opioids need to be carefully monitored, and patients should be educated very carefully on how to use them properly for shortness of breath.

There are a number of other pharmacologic agents that may be considered for selected populations, other than opioids. So if patients have a higher level of anxiety, then a short-acting benzodiazepine may be considered for those individuals. And for patients with more structural causes of shortness of breath, such as airway obstruction, systemic corticosteroids may be considered. And for patients with airway obstruction, then bronchodilators may be helpful as well, although the evidence around that is still on the weaker side.

And there are some patients who, despite very active intervention with many of these non-pharmacologic and pharmacologic measures, who continue to have very severe shortness of breath. And for those who are, let's say, in a palliative care unit setting and have refractory dyspnea, palliative sedation is mentioned as an option for patients as a last resort.

BRITTANY HARVEY: OK, thank you both for reviewing those interventions for patients. So Dr. Campbell, in your view, why is this guideline important? And how will it change practice?

DR. MARGARET CAMPBELL: Well, for a busy oncologic clinician who may not have a lot of time to search the literature because of a busy practice, what this puts in one place is an opportunity to do a quick guideline that could suggest a treatment course. For a palliative care provider, who may have more experience with non-cancer diagnoses, this guideline focuses on the patient with advanced cancer.

So I think there's an opportunity for clinicians in both of those fields who would be taking care of advanced cancer patients to find a benefit.

BRITTANY HARVEY: Definitely. And then finally, Dr. Hui, how will these guideline recommendations impact patients with advanced cancer?

DR. DAVID HUI: Yeah, well, I'd like to echo what Dr. Campbell said. I would also say that perhaps one of the strongest recommendations of this guideline is actually for patients with dyspnea and advanced cancer to be referred to palliative care. Because dyspnea is such a multi-dimensional symptom and often just the tip of the iceberg in terms of what patients are going through.

So just the very presence of it really highlights that there is likely a high supportive care burden, and it would be a good idea for a team specializing in relieving of this symptom to be there to work with the oncology team to help patients. So we hope that with this guideline, that there will be more patients who will have access to palliative care teams. And I think that will be one important impact. And there is a lot of evidence that palliative care can help our patients.

And other, maybe, impacts, I think, down the road for maybe future patients would be that we highlighted that more research is really needed in this field. The guideline clearly highlighted some areas we need to work on for further research. And it is not easy to do research in dyspnea and cancer patients because these patients are so sick. And yet these are the very patients who need to have better interventions.

And so with this guideline, we hope that it can stimulate further research and to support some patients in the future as well.

BRITTANY HARVEY: Great. Well, it definitely sounds like these will have a positive impact for both researchers and for patients with advanced cancer. So I want to thank you both for your work on these guidelines. And thank you for taking the time to talk with me today, Dr. Campbell, and Dr. Hui.

DR. DAVID HUI: It's my pleasure.

DR. MARGARET CAMPBELL: Mine also.

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/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.

Therapy for Stage IV Non–Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Guideline Update Feb 16, 2021

Show notes

An interview with Dr. Natasha Leighl, Dr. Andrew Robinson, and Dr. Gregory Riely on "Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO and OH (CCO) Guideline Update." This guideline provides recommendations on systemic therapy for patients with stage IV NSCLC whose cancer has driver alterations, focusing on seven targets - EGFR, ALK, ROS-1, BRAF V600e, RET, MET exon 14 skipping mutations, and NTRK. Read the full guideline at asco.org. TRANSCRIPT PRESENTER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. 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 podcasts.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. Natasha Leighl from Princess Margaret Cancer Center in Toronto, Ontario, Dr. Andrew Robinson from Queen's University in Kingston, Ontario, and Dr. Gregory Riely from Memorial Sloan Kettering Cancer Center in New York, New York, authors on Therapy for Stage IV Non-Small-Cell Lung Cancer with Driver Alterations: American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) Guideline Update. Thank you for joining me today, Drs. Leighl, Robinson, Riely. DR. ANDREW ROBINSON: Thank you for having us. DR. NATASHA LEIGHL: Thanks for having us, Brittany. 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. Leighl, do you have any relevant disclosures that are related to this guideline topic? DR. NATASHA LEIGHL: I don't have relevant disclosures, but I do have institutional research funding from a number of companies, including Amgen, ARRAY, AstraZeneca, EMD Serono, Guardant Health, Eli Lilly, Merck, Pfizer, Roche, and Takeda, and personal fees from Bristol-Myers and MSD, which are unrelated. Thanks. BRITTANY HARVEY: Thank you. And Dr. Robinson, do you have any relevant disclosures that are related to this guideline? DR. ANDREW ROBINSON: I do not have any relevant disclosures related to this guideline. My institutional list of research funding is not as extensive as Dr. Leighl's, but is still fairly extensive and includes many of those companies. BRITTANY HARVEY: And Dr. Riely, do you have any relevant disclosures? DR. GREGORY RIELY: I receive institutional research funding from Novartis, Roche, Genentech, GlaxoSmithKline, Pfizer, Moradi, Merck, and Takeda. But those are my only disclosures. BRITTANY HARVEY: Thank you all. Then let's get into some of the content of this guideline update. So this guideline is an update of an earlier ASCO guideline on the systemic treatment of patients with stage IV non-small cell lung cancer, which was then divided into two companion guidelines, one on systemic therapy treatment options for patients without driver alterations, which was published in 2020, and then this one for patients whose cancer has driver alterations. So Dr. Robinson, can you give us a general overview of what this particular guideline covers? DR. ANDREW ROBINSON: Thank you, Brittany. It was a great experience to be part of this important guideline and an honor. As you mentioned, this guideline is on treatment of stage IV non-small cell lung cancer patients with driver mutations. And it's a companion guideline to the earlier guideline published on treatment of stage IV non-small-cell lung cancer without driver mutations. The guideline followed a robust evidence gathering and evaluation process as a standard for ASCO-Ontario Health guidelines. In this case, we ended up reviewing several phase III trials, as well as many earlier phase studies and specific driver mutation groups. If we look back to 2017, there were four driver mutation group recommendations included in the guideline. We now have recommendations for seven different oncogenes, as well as some recommendations that are specific not only for the oncogene involved, but also the specific mutation within that gene. The non-driver mutation guideline is referenced as well frequently in this guideline, as many of the treatment options that are recommended in that guideline are also appropriate for patients with driver mutations, with the exception of a couple of key mutation groups such as EGFR. Recommendations in the guideline are qualified as weak, moderate, or strong, and the level of evidence for each recommendation is given. For many of these novel agents, the evidence is relatively low in comparison to what we are used to with recommendations based on phase II trials without comparator arms, and with surrogate endpoints for patient benefits such as response rates and duration of response, as opposed to quality of life and overall survival. Nonetheless, it was felt appropriate to include many of these agents in the recommendations, with the caveat that the level of evidence is weak or non-evidence-based. One of the recommendations in the introduction to these guidelines is to continue with studies such as phase III clinical trials in many of these settings, in order to move from an informal consensus-based recommendation, to a recommendation based on moderate to high quality evidence. We hope oncologists and their patients will find these guidelines useful. BRITTANY HARVEY: Great. Then, as you just mentioned, this guideline focuses on seven targets, EGFR, ALK, ROS1, BRAF, RET, MET, and NTRK. I'd like to review those key recommendations for each of those targets. So first, Dr. Robinson, what is recommended for patients with stage IV non-small-cell lung cancer and an epidermal growth factor receptor mutation? DR. ANDREW ROBINSON: Thank you. In terms of stage IV EGFR mutation positive lung cancer, the recommendations in the 2017 guidelines were to use tyrosine kinase inhibitors upfront, such as gefitinib, afatinib, or erlotinib, and to follow that with osimertinib if a mutation was found in T790M, or chemotherapy depending on what was available. In the current treatment guideline, we have recommendations not only for first and second line treatment, but also some acknowledgment and recommendations for treatment of patients with EGFR mutations other than the classical exon 19 deletion mutation or LA58R. For patients with a classical EGFR mutation, several strategies have been shown to be superior to first generation tyrosine kinase inhibitors in the first line setting. And the panel strongly recommended osimertinib to be used as first line therapy with a high level of evidence, based on the FLAURA clinical trial. This demonstrated not only an overall survival benefit, but a quality-of-life benefit. Other strategies that have been shown to benefit include dacomitinib as first line therapy, gefitinib plus chemotherapy as first line therapy. Erlotinib/bevacizumab and erlotinib/ramucirumab are also options with a lower level of evidence, as they have not been shown yet to be associated with improved overall survival. But they are associated with improved progression-free survival. Most of the recommendations, other than osimertinib, are really recommendations for what to pursue if osimertinib is not available. If we move to patients with sensitizing but non-classical EGFR mutations, the evidence is certainly much more sparse, as are these patients. And the recommendation was for afatinib first line or osimertinib was also considered an option based on phase II data. For patients with EGFR exon 20 insertion mutations, recommendation at this time was not to use a targeted agent first line, but to default to the non-driver mutation guidelines. For second line therapy, after tyrosine kinase inhibition stops benefiting, the recommendation was to use doublet platinum chemotherapy with or without bevacizumab. The atezolizumab/bevacizumab/carboplatin/paclitaxel combination was acknowledged as an option based on an exploratory analysis of the phase III EMPOWER trial, but this was considered exploratory and this regimen was not strongly recommended until further evidence accrues. BRITTANY HARVEY: OK, thank you. Then Dr. Leighl, what is recommended for patients with stage IV non-small-cell lung cancer and ALK rearrangement? DR. NATASHA LEIGHL: So for patients with ALK rearranged stage IV lung cancer, in the first line setting, next generation ALK inhibitors alectinib or brigatinib should be offered to patients. This is based on randomized trials comparing these to first generation inhibitors, crizotinib specifically, demonstrating better outcomes including progression-free survival and better intracranial activity. If you live in a region where alectinib and brigatinib are not available, earlier inhibitors like crizotinib or ceritinib should be offered again based on high quality evidence randomized trials demonstrating that these are better than chemotherapy. In the second line setting, if your patient has received alectinib or brigatinib first line, lorlatinib may be offered. If your patient received an earlier generation inhibitor crizotinib, they should be offered alectinib, brigatinib, or ceritinib, again based on randomized trials. And later, lorlatinib third line may be offered. It's also important to remember that in this group of patients, chemotherapy, especially pemetrexed-based chemotherapy, is very active. And we would refer you to the ASCO-Ontario Health non-driver mutation guidelines for chemotherapy recommendations when targeted therapy is no longer an option. I should also note that when we drafted these guidelines, we did not yet have results of the first line lorlatinib study, the CROWN study, where we found that lorlatinib was also superior to crizotinib, the first generation inhibitor. This is currently under review by the US FDA. So while it's not recommended in our guideline, we may see this added to future guidelines in our next guideline update. BRITTANY HARVEY: Great. Thank you. And then, what is recommended for patients with ROS1 rearrangement? DR. NATASHA LEIGHL: So for patients with ROS1 rearranged stage IV lung cancer, in the first line setting, specific ROS1 inhibitors, crizotinib or entrectinib may be offered. Because this is based on very impressive response rates and prolonged duration of response and patient benefit, in single arm studies, we have to recognize that alternatives may also include standard treatment based on the ASCO non-driver mutation guidelines, as well as other target agents, such as ceritinib or lorlatinib, that may be offered. If, though, your patient has progressive disease and previously received non-targeted therapy, targeted therapy with crizotinib, ceritinib, or entrectinib, can certainly be offered. Also, if your patient has received ROS1 targeted therapy in the first line setting, standard treatment based on the ASCO non-driver mutation guidelines should be offered also with consideration of clinical trials. BRITTANY HARVEY: And then additionally, what is recommended for patients with stage IV non-small-cell lung cancer and an NTRK fusion? DR. NATASHA LEIGHL: Thanks, Brittany. For patients with stage IV disease and an activating NTRK fusion, entrectinib or larotrectinib may be offered in the first line setting based on single arm studies, including patients with lung cancer and very dramatic response rates and prolonged duration of response. However, standard treatment based on the non-driver mutation guideline chemotherapy-based may also be offered in the second line setting. If NTRK targeted therapy was given first line, standard treatment with chemotherapy-based options may be offered second line based on the non-driver mutation guideline. If NTRK targeted therapy, though, was not given in the first line setting, entrectinib or larotrectinib may be offered to your patient. And I think at this point, we really don't know what the optimal sequence is for these patients. But I think it's very clear from the data that we do have, that we want to try and identify this target and get patients on targeted therapy as soon as possible in the course of their disease. BRITTANY HARVEY: Great. Then Dr. Riely, can you review what the guideline recommends for patients with stage IV non-small cell lung cancer and a BRAF mutation? DR. GREGORY RIELY: Thank you, Brittany. I'll highlight that the BRAF mutation guideline pertains specifically to those patients with BRAF V600E mutations. The other BRAF mutations that we observed, we don't have sufficient data to make recommendations. But for those patients with BRAF V600E alterations, again, based on the quality of the data and the type of data available, the guidelines recommend consideration of first line use of dabrafenib with trametinib. This is a consideration rather than a should recommendation, given the absence of randomized clinical trial evidence. But nonetheless, we recommend that they be considered in the first line setting. If, in fact, you choose to use a non-targeted approach in the first line setting, then the guidelines do recommend consideration of dabrafenib with trametinib in the second line setting. So it's, again, the first line setting, dabrafenib/trametinib combination. Or, if not used in the first line setting, then recommendation dabrafenib/trametinib in the second line setting. BRITTANY HARVEY: OK, then, what is recommended for patients with stage IV non-small-cell lung cancer and a MET mutation? DR. GREGORY RIELY: Again, specific for MET, we're talking about MET exon 14 alterations rather than MET amplification with other mutations, which we might call emerging targets. So for patients with metastatic exon 14 altered non-small cell lung cancer, the recommendation is for the use of capmatinib or tepotinib. These are newer MET inhibitors that have recently been approved. And again, the guidelines recommend that they should be considered in the first line setting. If, however, you choose to use non-targeted therapies in the first line setting, then MET directed therapy such as capmatinib or tepotinib should be considered in the second line setting. BRITTANY HARVEY: And then the final target addressed in this guideline, what is recommended for patients with stage IV non-small cell lung cancer and RET rearrangement? DR. GREGORY RIELY: RET rearrangements are relatively uncommon, but important in a subset of patients with non-small cell lung cancer. And we have MET targeted agents that are available. The current guidelines recommend that in the first line setting, we consider the use of selpercatinib. And in the second line setting, if patients have not previously received a RET inhibitor, one should consider selpercatinib in that context. Patients who have received a targeted therapy in the first line then conventional chemotherapy with or without immunotherapy or bevacizumab should be considered. I will note that the guidelines were finalized prior to the approval of pralsetinib, and pralsetinib is another RET inhibitor with similar data in this context. BRITTANY HARVEY: Great. Thank you all for reviewing those recommendations. So Dr. Robinson alluded to this earlier, but Dr. Riely, could you describe what emerging targets the panel reviewed but were unable to make recommendations for…

Full show notes at the publisher

Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer Guideline Jan 28, 2021

Show notes

An interview from Dr. Larissa A. Korde from the National Cancer Institute and Dr. Dawn L. Hershman from Columbia University on "Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline." This guideline covers the optimal use of neoadjuvant therapy for women with invasive, non-metastatic breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines.

Transcript

ASCO: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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 podcast.asco.org.

My name is Brittany Harvey, and today I am joined by Dr. Larissa Korde from the clinical investigations Branch of the Cancer Therapy Evaluation Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute in Bethesda, Maryland, and Dr. Dawn Hershman from the Herbert Irving Comprehensive Cancer Center at Columbia University in New York, New York, co-chairs on Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline. Thank you for being here Dr. Korde and Dr. Hershman.

DR. LARISSA KORDE: Thank you for having us.

DR. DAWN HERSHMAN: Yes, thank you.

BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines in 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 on-line with the publication of the guideline in the Journal of Clinical Oncology. Dr. Korde, do you have any relevant disclosures that are related to this guideline topic?

DR. LARISSA KORDE: I do not.

BRITTANY HARVEY: And Dr. Hershman, do you have any relevant disclosures that are related to this guideline topic?

DR. DAWN HERSHMAN: No, I do not.

BRITTANY HARVEY: Great, thank you both. Then, Dr. Hershman, to kick off the content of the guideline, first, can you give us a general overview of the scope and the purpose of this guideline?

DR. DAWN HERSHMAN: Yeah, sure. In breast cancer, we have seen a plethora of studies looking at neoadjuvant therapy for breast cancer. And as we've learned over time, that neoadjuvant therapy has focused on the role of, really, response as a predictive marker and whether or not the improvement in a pathologic complete response rate translates into benefit in terms of long-term outcome. And the fact that several studies have shown that has really increased our interest in looking at pathologic complete response rate and its predictive value.

So part of the guideline is really to help us really elucidate as the understanding of biology of breast cancer has evolved over time, what scenarios where neoadjuvant therapy is the best choice for patients, and what the real purpose of neoadjuvant therapy is. So the guidelines' purpose is really to help us develop recommendations concerning the optimal use of neoadjuvant therapy, whether it be chemotherapy, endocrine therapy, or targeted therapy for a variety of different biologic subtypes. And I think the overarching principle is that the expert panel strongly advocated for a multidisciplinary team in the management of these patients. Specific guidelines really go into details about each of the scenarios where we would use this therapy.

BRITTANY HARVEY: Great. Then I'd like to review some of those key recommendations that you just mentioned for our listeners. So Dr. Korde, which patients with breast cancer are appropriate candidates for neoadjuvant systemic therapy?

DR. LARISSA KORDE: So when we sat down to write this guideline, we thought through this question in many different ways. But we basically ended up sort of dividing patients by breast cancer subtype and then coming up with recommendations separately for each subtype. So broadly speaking for triple negative breast cancer patients and for HER2-positive breast cancer patients, we felt that the kind of most important triage point is that in both those diseases, there are effective treatments that can be used in the adjuvant setting in patients who do not have a pathologic complete response to neoadjuvant therapy. And so broadly speaking, it's those patients where there would be an adjuvant therapy decision point, or recommendation in whom the neoadjuvant response is important. Those would be the patients in whom we would most strongly recommend neoadjuvant chemotherapy.

In ER-positive disease, we looked at both chemotherapy and endocrine therapy in the neoadjuvant setting. And we know that both of these can improve response. Pathologic complete response is less common in patients with ER-positive disease. But there are also benefits to neoadjuvant treatment in those patients in terms of being able to reduce the size of the surgery, reduce potentially morbidity from surgery, and then also in terms of being able to convert patients who were not lumpectomy candidates from mastectomy to lumpectomy. And so in the guideline we outline the scenarios for ER-positive patients in which neoadjuvant therapy would be recommended as well.

BRITTANY HARVEY: Great, got it. Then Dr. Hershman, what do the guidelines say about how clinicians should measure response in patients receiving neoadjuvant chemotherapy?

DR. DAWN HERSHMAN: Yes, so patients undergoing neoadjuvant therapy should really be monitored by their provider at each visit with a clinical examination at regular intervals. And we really felt that the role of breast imaging was really for patients where there was some clinical suspicion of progression during that therapy to ensure that patients were not progressing during treatment. And ultimately, the best modality for imaging was the modality that was most effective at the point of diagnosis, whether it be mammogram, ultrasound, or MRI, that should be the imaging modality used at follow up.

We did not feel that there were any specific blood markers or tissue based markers at this time that should be used for monitoring patients undergoing neoadjuvant therapy. Much of that is done for clinical trial purposes, but not so much in the clinic. And that when patients had completed their treatment, pathologic complete response rate is the most important outcome and would be really assessed at the time of surgery as the absence of any invasive disease in either the breast or the lymph nodes.

But in order for that to be good for clinical decision making, it's really imperative that the clinician and the surgeons make sure that the tissue is removed that is suspect to begin with, so to make sure that the clips that defined where the tumor was evaluated and that the tumor bed is clear of any evidence of disease.

BRITTANY HARVEY: Great, that's helpful information. So then, Dr. Korde, you mentioned that the recommendations are divided up by biologic subtypes. So what are those neoadjuvant systemic therapy regimens recommended for the following patient population-- so first, those with triple negative breast cancer, second, those with HER2-negative hormone receptor positive breast cancer, and then finally, for those with HER2-positive disease?

DR. LARISSA KORDE: So maybe we can divide this up a little. Let's start with the triple negatives. For triple negative breast cancer patients who are embarking on neoadjuvant chemotherapy, and that would be patients with clinically node positive disease, and/or at least T1C disease, and again, with the thought that the goal is really to think about whether adjuvant therapy recommendations would be altered based on PAP CR. But in that setting, we recommended that patients be offered an anthracyclines and taxane containing regimen.

We also found data supporting the use of carboplatin with neoadjuvant therapy for the purpose of increasing the likelihood of PCR. So we noted that while there is good data showing that PCRs increase with carboplatin, there is more conflicting data regarding the effect of carboplatin on long-term outcomes. Although, hopefully, new clinical trials that are ongoing now or that are in follow up may clarify this question a little bit more.

We felt at the time that we wrote the guideline, and certainly, this is potentially an evolving topic. But at this point, we felt that there was insufficient evidence to recommend routinely adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early stage breast cancer. And again, there may be more data on this upcoming in the next few years. So maybe Dawn can take the next category, the HER2-negative hormone receptor positive patients.

BRITTANY HARVEY: Yeah, that would be great.

DR. DAWN HERSHMAN: Absolutely. So we felt for this population of patients that neoadjuvant chemotherapy could be used instead of adjuvant chemotherapy in any patient where the chemotherapy decision could be made without the benefit of having the results from the surgical pathology data, or any results from the specific genomic testing. So if the decision was made that the patient was going to need chemotherapy regardless, that would be a patient that could get it neoadjuvantly.

We felt that for postmenopausal patients with hormone receptor positive HER2 negative breast cancer that neoadjuvant endocrine therapy with an aromatase inhibitor could be offered to either increase local regional treatment options, if there was no intent for surgery, endocrine therapy could be used for Disease Control. So in a patient where they really were not a good surgical candidate, we could offer this therapy to try to control their disease. For premenopausal patients with hormone receptor positive HER2-negative disease, we did really not feel that neoadjuvant endocrine therapy should be routinely offered outside of a clinical trial. Because in this scenario, there really wasn't enough evidence to offer this approach.

BRITTANY HARVEY: And then Dr. Korde, do want to finally address those patients with HER2-positive disease?

DR. LARISSA KORDE: Absolutely. So in patients with HER2-positive disease that is either node positive or high risk node negative, we felt it would be appropriate to offer neoadjuvant therapy with either an anthracycline and taxane containing regimen, or a non-anthracycline-based regimen in combination with targeted therapy. And we did feel that targeted therapy should include trastuzumab and may also include pertuzumab. For patients with smaller tumors, really those in whom it's unclear whether the more aggressive for on-chemotherapy regimens or even any chemotherapy at all is needed, for example, those with very small tumors, T1A and T1B, we did not feel that neoadjuvant should be routinely offered. And we did note that in those patients with smaller tumors, an alternative regimen, the APT regimen of paclitaxel and Trastuzumab is something that has been studied in the adjuvant setting. But again those patients with these very small node negative tumors, in general, would not be routinely offered neoadjuvant chemotherapy.

BRITTANY HARVEY: Great, thank you both for reviewing those neoadjuvant systemic therapy approaches for those specific patient populations. So Dr. Hershman, in your view, what is the importance of this guideline? And how will it impact clinical practice?

DR. DAWN HERSHMAN: Yeah, that's an excellent question. I think as our data has shown more and more studies where there's a benefit to giving adjuvant treatment based on the response of patients in the neoadjuvant setting to get additional benefit long-term amongst patients with residual disease, I think that these guidelines really can help clinicians to understand those scenarios where we know we can maximize treatment.

I think ultimately the goal of neoadjuvant therapy is that it gives us opportunities to both escalate treatment in patients that are at high risk that don't have great responses, and de-escalate therapy in patients that have outstanding responses. And so I think this will help clinicians understand what those benefits are.

BRITTANY HARVEY: Definitely. It seems like it will provide some clarity for those scenarios. So finally, Dr. Korde, how do you envision that these guideline recommendations will affect patients with non-metastatic breast cancer?

DR. LARISSA KORDE: Well, I think building on Dr. Hershman's answer to the previous question, really, the key here is to be able to personalize or tailor the therapy for individual patients. So in those patients whose disease is very high risk, or did not respond to initial therapy, patients can be given appropriate escalation of treatment. And for patients who have an excellent response to treatment in the neoadjuvant setting can potentially be spared other treatments. And so I think that the main use of neoadjuvant treatment and the use of this guideline in terms of how it affects patients is being able to offer the most appropriate therapy for each patient.

BRITTANY HARVEY: Great, well, thank you both for your work on this guideline on neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer. Appreciate your leadership on this guideline. And I want to thank you also for taking the time to speak with me today, Dr. Korde and Dr. Hershman.

DR. DAWN HERSHMAN: Thank you.

DR. LARISSA KORDE: Happy to be here. Thanks so 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.

Radiation Therapy for Small Cell Lung Cancer Guideline Endorsement Jan 27, 2021

Show notes

An interview with Dr. Megan E. Daly from the University of California, Davis on "Radiation Therapy for Small Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline." An ASCO Expert Panel reviewed an ASTRO guideline on radiation therapy for SCLC and determined it was clear, thorough, and evidence based. ASCO endorsed the ASTRO guideline with a few discussion points, which Dr. Daly reviews in this podcast. Read the full guideline endorsement at www.asco.org/thoracic-cancer-guidelines.

TRANSCRIPT

PRESENTER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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 podcast.asco.org. My name is Brittany Harvey, and today, I'm interviewing Dr. Megan Daly from the University of California Davis, Co-Chair and lead author on "Radiation Therapy for Small Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline."

Thank you for being here, Dr. Daly.

DR. MEGAN DALY: Thank you. Glad to be here.

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 panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Daly, do you have any relevant disclosures that are directly related to this guideline topic?

DR. MEGAN DALY: I do not.

BRITTANY HARVEY: Great. Thanks so much. So generally, can you give us an overview of what this guideline endorsement addresses and how the ASCO guideline endorsement process works?

DR. MEGAN DALY: This guideline was designed to provide an endorsement of a very comprehensive guideline provided by the American Society of Radiation Oncology addressing the use of radiation therapy for small cell lung cancer. The guideline endorsement process involved us developing a team of physicians, both medical oncologists and radiation oncologists, to review and assess the ASTRO guideline and make recommendations and clarifications for the ASCO audience.

So our guideline panel met several times by teleconference. We carefully reviewed the guidelines with assistance from the ASCO staff. We reviewed each individual recommendation within the ASTRO guideline, including the supporting evidence and the final recommendations, and provided clarifying comments, when necessary.

The entire guideline panel had to vote and reach a consensus on each individual recommendation from the ASTRO guideline to form a final consensus. And ultimately in the case of this guideline, we largely agreed with the excellent ASTRO guideline that had already been produced. So this was largely a process of confirming and endorsing ASTRO's guideline product. We also, then, provided a written paper that provides some additional clarification in context for ASCO's audience.

BRITTANY HARVEY: Great. So you just touched on some of the recommendations of the guidelines. So what were those key recommendations of this guideline?

DR. MEGAN DALY: So this guideline was specifically addressing the use of radiation therapy for small cell lung cancer, both limited-stage and extensive-stage small cell lung cancer. So the key recommendations that came out of both the ASTRO guideline and ASCO's recommendation of ASTRO's guidelines were first that radiation therapy should be used for most patients with limited-stage small cell lung cancer, confirming standard practice, and that doses of 45 gray in twice daily fractionation remain the standard of care, but alternative schedules delivering 60 to 70 gray over a single fraction are also reasonable.

The guideline also addressed that stereotactic radiation is an appropriate consideration for early-stage node-negative limited-stage small cell lung cancer. The guideline also addresses the use of prophylactic cranial irradiation and continues to recommend the use of prophylactic cranial irradiation for fit patients with limited-stage small cell lung cancer while recommending shared decision making for other patients, including those with extensive-stage disease or patients who might have contraindications to PCI for limited-stage small cell lung cancer. And finally, the guideline also addressed the use of consolidated thoracic radiation in extensive-stage small cell lung cancer, providing a recommendation that it be considered for well-selected patients with extensive-stage disease.

BRITTANY HARVEY: OK, and then you mentioned earlier that there were select scenarios in which the panel offered clarifying comments. So in which sections did the ASCO expert panel decide to offer those clarifying comments?

DR. MEGAN DALY: Our clarifying comments were largely simply to provide clarification in several of the recommendations. For example, in recommendation 1.2, where ASTRO recommends that it's important to maintain the dosage and timing of chemotherapy with radiation and that timing is more critical for accelerated dose intensive radiation, we clarified that dose intensive radiation would be referring to twice daily hyper-fractionated regimens.

We also provided clarification that ultracentral tumors refer to those where a planning target volume is overlapping or touching the proximal bronchial tree, the esophagus, and trachea within the recommendation that those tumors, even when early stage might better be addressed by fractionated, rather than a stereotactic radiation.

And finally, for recommendation 4.4, it states for patients with extensive-stage small cell with a response to chemotherapy and immunotherapy and residual disease in the thorax, thoracic radiation to 30 gray and 10 fractions within six to eight weeks can be considered. And we provided clarification that that would be six to eight weeks of completion of the chemotherapy and prior to maintenance immunotherapy.

BRITTANY HARVEY: Great. Then it sounds like those notes will be key for the ASCO audience in interpreting and implementing these recommendations. So in your view, what is the importance of this guideline endorsement? And how will it affect ASCO members?

DR. MEGAN DALY: So I believe this guideline endorsement and the initial ASTRO guideline are both very important in providing guidance to both radiation oncologists and medical oncologists who routinely treat small cell lung cancer patients in their practice. The small cell lung cancer space is constantly changing, and there have been some major developments in small cell lung cancer within the last 5 to 10 years, most notably surrounding the use of prophylactic cranial irradiation and extensive-stage disease.

There's also a number of interesting ongoing clinical trials looking at the use of consolidated thoracic radiation in extensive-stage disease. And many practitioners have questions about how to use radiation in the landscape of changing systemic therapies, for example, the integration of immunotherapy into extensive-stage disease, as well as how to integrate newer irradiation technologies like stereotactic radiation into the treatment of small cell lung cancer. So I believe that this guideline endorsement, as well as the original guidelines, can provide valuable guidance to the ASCO community in how to treat these patients in their daily practice.

BRITTANY HARVEY: Great. And then finally, how do these guideline recommendations impact patients with small cell lung cancer?

DR. MEGAN DALY: Hopefully, these guideline recommendations will help patients with small cell lung cancer receive standard of care latest treatments incorporating radiation. And there's a number of areas where radiation has been shown to improve survival in small cell lung cancer. So we absolutely want to make sure that our patients are receiving the best possible care that incorporates all available treatment modalities and incorporates all the latest data.

BRITTANY HARVEY: Great. Well, thank you so much for your work on this guideline endorsement, and thank you for taking the time to speak with me today, Dr. Daly.

DR. MEGAN DALY: Yeah, Brittany, thank you so much. Glad to be here.

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/thoracic-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.

Initial Management of Non-Castrate Advanced, Recurrent, or Metastatic Prostate Cancer Guideline Update Jan 26, 2021

Show notes

An interview with Dr. Katherine S. Virgo from Emory University in Atlanta, GA on "Initial Management of Non-Castrate Advanced, Recurrent or Metastatic Prostate Cancer: ASCO Guideline Update." This guideline updates recommendations for initial hormonal management of non-castrate advanced, recurrent, or metastatic prostate cancer. Read the full guideline at www.asco.org/genitourinary-cancer-guidelines.

TRANSCRIPT

PRESENTER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Katherine Virgo from Emory University, lead author and co-chair on initial management of non-castrate advanced, recurrent, or metastatic prostate cancer, ASCO guideline update. Thank you for being here, Dr. Virgo.

DR. KATHERINE VIRGO: Thank you, Brittany.

DR. KATHERINE VIRGO: No, I do not.

BRITTANY HARVEY: OK, thanks. Then let's delve into some of the guideline content. What prompted this update of the initial management of non-castrate advanced, recurrent, or metastatic prostate cancer guideline, and what is the scope of the update?

DR. KATHERINE VIRGO: Well, the update of the 2007 version of the guideline was largely prompted by the many Phase III randomized clinical trials that had been completed or were nearly complete in the non-castrate space. It was believed that the results of these trials might permit revisiting previous recommendations regarding intermittent versus continuous androgen deprivation therapy and early or immediate versus deferred androgen deprivation therapy.

As you might imagine, it took quite some time to gather and review 13 years of literature for each of the study questions from the original 2007 guideline. So in the interim, a sufficient number of randomized clinical trials reached completion to also inform recommendations regarding the use of newer therapies in combination with androgen deprivation therapy as initial therapy for men with metastatic disease, such as docetaxel, abiraterone, enzalutamide, and apalutamide, and thereby also update another existing ASCO guideline authored by Morris et al in 2018, which previously only provided guidance on the use of docetaxel and abiraterone for men with metastatic disease.

BRITTANY HARVEY: Great, yeah, definitely a large volume of literature to review there. So then you talked about the recommendations. So I'd like to go through some of those. For men with metastatic non-castrate prostate cancer, what are the recommended standard initial treatment options?

DR. KATHERINE VIRGO: So docetaxel, abiraterone, enzalutamide, and apalutamide, each when administered with androgen deprivation therapy, represent four separate standards of care for non-castrate metastatic prostate cancer. The use of any of these agents in any particular combination or in any particular series cannot yet be recommended. That said, we were able to make a recommendation for each agent individually. So I'll go through those recommendations now, first for docetaxel.

So for men with metastatic non-castrate prostate cancer with high-volume disease who are candidates for treatment with chemotherapy, the addition of docetaxel to androgen deprivation therapy should be offered. Here, high-volume disease is defined per the charted trial as four or more bone metastases, one or more of which is outside of the spine or pelvis, and/or the presence of any visceral disease.

Second, for abiraterone, for men with high-risk de novo metastatic non-castrate prostate cancer, the addition of abiraterone to androgen deprivation therapy should be offered per the latitude trial. For men who are considered low-risk, androgen deprivation therapy plus abiraterone may be offered for the STAMPEDE trial.

Third, for enzalutamide, androgen deprivation therapy plus enzalutamide should be offered to men with metastatic non-castrate prostate cancer, including those with de novo metastatic disease and those who have received prior therapies, such as radical prostatectomy or radiation therapy for localized disease. Enzalutamide plus ADT has demonstrated short-term survival benefits, such as PSA progression-free, clinical progression free, and overall survival when compared to androgen deprivation therapy alone for men with metastatic non-castrate prostate cancer per the ENZAMET trial.

And finally, fourth, androgen deprivation therapy plus apalutamide should be offered to men with metastatic non-castrate prostate cancer, including those with de novo metastatic disease or those who have received prior therapy, such as radical prostatectomy or radiation therapy for localized disease, per the TITAN trial. Thus in summary, to your initial question, all of the recommendations were phrased as "should be offered" except in the case of androgen deprivation therapy plus abiraterone for men with low-risk de novo metastatic non-castrate prostate cancer, for which the recommendation was phrased as "may be offered," as the evidence was not as strong as for the other recommendations.

BRITTANY HARVEY: Great, thank you for reviewing those standard initial treatment options for men with metastatic non-castrate prostate cancer. So then what does the guideline say regarding combination therapy for men with non-castrate locally advanced non metastatic prostate cancer?

DR. KATHERINE VIRGO: So here, androgen deprivation therapy plus abiraterone and prednisolone should be considered for men with non-castrate locally advanced non-metastatic prostate cancer, rather than castration monotherapy, due to the failure-free survival benefit for the STAMPEDE trial. We were unable to make a recommendation for men with high-risk non-metastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both, as it's currently unclear whether enzalutamide in the 160-milligram dose plus leuprolide improved metastasis-free survival compared to enzalutamide monotherapy or placebo. The recruitment is complete for the ongoing Phase III EMBARK trial, which is designed to answer this question. The results are not available yet.

BRITTANY HARVEY: Great. Then how does the guideline address early or immediate androgen deprivation therapy versus deferred therapy for men with non-castrate locally advanced non-metastatic prostate cancer?

DR. KATHERINE VIRGO: So here, early or immediate androgen deprivation therapy may be offered to men who initially present with non-castrate locally advanced non-metastatic disease who have not undergone previous local treatment, and are either unwilling or unable to undergo radiotherapy, based on evidence in one meta-analysis of a modest but statistically significant benefit in terms of both overall survival and cancer-specific survival among the larger population of men with locally advanced non-metastatic disease. Unfortunately, we were unable to make a recommendation for men with PSA relapse after local treatment. Though existing studies suggest a potential overall survival benefit, additional research is needed, as such studies were underpowered.

BRITTANY HARVEY: And then finally, for men with biochemically recurrent non-metastatic disease, what are the recommendations for intermittent androgen deprivation therapy versus continuous androgen deprivation therapy?

DR. KATHERINE VIRGO: So intermittent therapy may be offered to men with high-risk, biochemically recurrent non-metastatic prostate cancer after radical prostatectomy and/or radiotherapy, based on evidence and meta-analyses of the non-inferiority of intermittent androgen deprivation therapy when compared to continuous androgen deprivation therapy, with respect to overall survival. This is further supported by evidence from four meta-analyses testing superiority. And here, high-risk biochemical recurrence after radical prostatectomy is defined as a PSA doubling time less than one year or a pathologic Gleason score of 8 to 10. High-risk biochemical recurrence after radiation therapy has a different definition, here defined as an interval to biochemical recurrence of less than 18 months or a clinical Gleason score of 8 to 10.

BRITTANY HARVEY: Thank you for reviewing all those recommendations and the evidence supporting them. It's very interesting to hear where you were able to make recommendations and where you weren't. So in your view, what is the importance of this guideline, and how will it change practice?

DR. KATHERINE VIRGO: As mentioned earlier, the previous version of the guideline was 13 years old. And practice, as you might imagine, has changed considerably in the interim. Though consensus documents have been issued by other organizations since that time, it was important, given ASCO's global audience, to provide up-to-date, evidence-based guidance for the organization's worldwide membership.

Practice patterns of most clinicians based at large university medical centers likely approximate the guidance provided in the ASCO guideline update, at least with respect to the treatment of men with de novo metastatic high-risk or high-volume disease. Some may be surprised by the current lack of evidence for the use of docetaxel among patients with de novo metastatic low-volume disease. The new guidelines should be particularly useful for community-based clinicians, who may not be as actively involved in clinical trial enrollment.

BRITTANY HARVEY: Definitely. And then finally, how will these guideline recommendations impact patients with prostate cancer?

DR. KATHERINE VIRGO: So patients will be impacted in three ways. First, the guidelines should be helpful to patients in understanding the various treatment options available to them, depending on the extent of their disease and any previous treatment they may have already received. The guidelines also highlight treatment options that should not be offered to patients who have certain characteristics and hopefully assist patients with adjusting their treatment expectations.

Second, the cost table in the guidelines should also be helpful to patients, as it provides some idea of how costs vary by the type of treatment received, while also indicating when a less costly generic equivalent is available. And finally, third, the guidelines suggest that patients be counseled about the potential side effects associated with androgen deprivation therapy, such as depression, dementia, stroke, myocardial infarction, deep venous thrombosis, hot flush, fatigue, and nausea. Side effects vary by type of androgen deprivation therapy, as well as by age and patient comorbidities. Knowing up-front that such side effects are possible can assist patients in having more informed conversations with their physician when treatment discussions are underway.

BRITTANY HARVEY: Great. Then it sounds like these guidelines have a real impact for both community oncologists and for patients. So I want to thank you for your leadership on the development of these evidence-based guidelines, and thank you for taking the time to speak with me today, Dr. Virgo.

DR. KATHERINE VIRGO: Thank you, Brittany.

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 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.

PREVIEW: ASCO in Action CEO & CMO Interview Jan 19, 2021

Show notes

A preview of the interview by ASCO in Action podcast host ASCO CEO Dr. Clifford A. Hudis with retiring ASCO Chief Medical Officer Dr. Richard L. Schilsky examining Dr. Schilsky's trailblazing medical career, his leadership in ASCO and indelible mark on its research enterprise, and what he sees for the future of oncology. Dr. Hudis also shares what Dr. Schilsky's friendship and mentorship has meant to him and suggests that he will still be supporting ASCO on critical priorities. Find all nine of ASCO's podcasts and subscribe at podcast.asco.org.

TRANSCRIPT

Dr. Clifford Hudis: Hello, I'm Dr. Clifford Hudis, CEO of ASCO, dropping into your feed to let you know about a special episode of the ASCO in Action podcast featuring the extraordinary career of Dr. Richard Schilsky, ASCO's Chief Medical Officer. Rich and I discuss the advances that have revolutionized cancer care over the last 50 years and much, much more. Here's a preview of the episode.

Dr. Richard Schilsky: The 1980s in many respects were the doldrums of progress in clinical oncology. There really was not a lot of innovation in the clinic. But what was happening and what was invisible to many of us, of course, was that was the decade of discovery of the fundamental biology of cancer. That's when oncogenes were discovered, when tumor suppressor genes were discovered, when it became clear that cancer was really a genetic disease. And that is what transformed the field and put us on the path to targeted therapy and precision medicine as we think of it today.

Dr. Clifford Hudis: You can find the ASCO in Action Podcast on Apple Podcasts or wherever you are listening to this show. And you can find all nine of ASCO's podcasts which cover a wide range of educational and scientific content and offer enriching insight of the world of cancer care at podcast.asco.org.

Chemotherapy in Combination with Radiotherapy for Definitive-intent Treatment of Stage II to IVA Nasopharyngeal Carcinoma: CSCO-ASCO Guideline Jan 06, 2021

Show notes

An interview with Dr. Jun Ma from Sun Yat-sen University Cancer Center in Guangzhou and the Chinese Society of Clinical Oncology on "Chemotherapy in Combination with Radiotherapy for Definitive-intent Treatment of Stage II to IVA Nasopharyngeal Carcinoma: Chinese Society of Clinical Oncology and American Society of Clinical Oncology Guideline." Read the full guideline at www.asco.org/head-neck-cancer-guidelines.

Transcript

ASCO: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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 podcast.asco.org.

My name is Brittany Harvey, and today I'm interviewing Dr. Jun Ma from Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy in Guangzhou, and the Chinese Society of Clinical Oncology, author on Chemotherapy in Combination with Radiotherapy for Definitive-intent Treatment of Stage II to IVA Nasopharyngeal Carcinoma, Chinese Society of Clinical Oncology and American Society of Clinical Oncology Guideline. Thank you for being here today, Dr. Ma.

JUN MA: Yes.

BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines in 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. Ma, do you have any relevant disclosures that are directly related to this guideline topic?

JUN MA: Thank you, Brittany. Hi, everyone. I'm Dr. Jun Ma from the Sun Yat-sen University Cancer Center in China. And I don't have any potential conflicts of interest related to this guideline topic.

BRITTANY HARVEY: Great. Thank you. Then can you give us a general overview of what this guideline covers?

JUN MA: Yes. This guideline aims to highlight significant clinical questions about the chemotherapy in combination with the radiotherapy for the definitive treatment of stage II to stage IVA NPC, nasopharyngeal carcinoma, It will clarify the fundamental principles of the radiotherapy planning and how to combine chemo with radiotherapy for a patient's success.

BRITTANY HARVEY: Great. Then this guideline covers five clinical questions. I'd like to review those key recommendations for our listeners. First, what does the guideline state regarding radiotherapy for patients with stage II to IVA nasopharyngeal carcinoma?

JUN MA: Yes. For all nasopharyngeal carcinoma patients, we support the use of IMRT summarized in the current evidence. We don't recommend the use of other techniques, such as 2D or even 3D radiotherapy. If IMRT is not available at that spot, patients should be transferred to the institution that could that could implement IMRT whenever possible.

For all NPC patients, a prescribed dose of 70 Gy in 33 or 35 fractions delivered over seven weeks should be offered. It should be noted that the radiation dose may be adjusted according to the tumor volume and its response to the chemoradiotherapy. In terms of the target delineation, we recommend you to follow several existing consensus guidelines. Thank you.

BRITTANY HARVEY: OK. Then what is recommended regarding chemotherapy sequence in addition to radiotherapy?

JUN MA: OK, generally speaking, patients with low disease burden, such as the lower end category of clinical stage, could receive lower intensity of chemotherapy. For T2, and if not negative of patients, chemotherapy is not routinely recommended, while for T1 or 2, N1 patients concurrent chemotherapy may be offered, particularly for T2 N1 patients.

For locoregional advanced disease, except the T3 lymph node negative patients, we recommend the use after concurrent chemotherapy with induction or adjuvant chemotherapy. It should be noted that there is a lack of head-to-head trials comparing induction chemo plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy plus adjuvant chemo. Thus, which sequence performs better in the contemporary era remains uncertain.

Finally, for T3 lymph node-negative patients, concurrent chemoradiotherapy should be offered. Adjuvant or induction chemotherapy may also be offered if there are adverse features, such as the bulky tumor volumes or high EBV DNA copy numbers.

BRITTANY HARVEY: Great. Then you just mentioned some chemoradiotherapy regimens. So for patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy, what are the recommended chemotherapy options?

JUN MA: OK, for all NPC patient without contraindications, concurrent cisplatin should be offered along with radiotherapy. Weekly use after suspending with 48 milligrams per square meter or three weekly with eight or 200 milligram per square meter is acceptable. We recommended the cisplatin dose should be attempted to achieve a cumulative dose of at least 200 milligrams per square meter.

For patients with contraindications to cisplatin, nedaplatin, carboplatin, or oxaliplatin may be alternative choice. For patients with contraindications to cisplatin-based chemotherapy, Fluoropyrimidines such as 5FU with concurrent chemotherapy also may be offered. Thank you.

BRITTANY HARVEY: Great. And then for patients with nasopharyngeal carcinoma receiving induction chemotherapy, what are those recommended options?

JUN MA: Yes. For all patients receiving induction or adjuvant chemotherapy, platinum-based induction regimens should be offered in terms of induction chemo, such as GP, TPF, TP, PF, and the PX regimens are recommended. So induction regimens should be administered every three weeks for a total of three cycles, or at least the minimum two cycles. If the patients receive induction chemotherapy, chemoradiotherapy should be commenced within 21 to 28 days from the first day of the last cycle of induction chemotherapy.

BRITTANY HARVEY: Great. And then for the final set of recommendations for patients with nasopharyngeal carcinoma receiving adjuvant chemotherapy, what are those recommended chemotherapy options?

JUN MA: Considering that adjuvant chemotherapy is a choice of adjuvant regimens were much fewer than those of induction chemotherapy, according to current evidence. PF regimen administered every four weeks for a total of three cycles is recommended. If with contraindication to cisplatin, carboplatin may be combined with 5-FU.

It should be noted that for all patients receiving adjuvant chemotherapy and with contraindications to platinum-containing chemotherapy, the use of non-platinum based regimens remain experimental at this time and should not be offered routinely outside of the context of a clinical trial. The main difference between the recommendation for the induction and adjuvant chemotherapy are primarily due to the number of the randomized trials in which there are few studies regarding the adjuvant chemotherapy in nasopharyngeal carcinoma. Thank you.

BRITTANY HARVEY: Thank you for reviewing each of those recommendations. So then, what is the importance of this guideline? And how will it impact clinical practice in patients with nasopharyngeal carcinoma?

JUN MA: For nasopharyngeal carcinoma, it has extremely uneven geographically global distribution. More than 70 percent of this new diagnosis worldwide in the 2018 year, occurred in the East and Southeast Asia. Therefore, nasopharyngeal carcinoma remains a significant public health problem in these regions, which emphasize the significance of this guideline for providers and patients from the endemic area.

From my point of view, one of the novel features of this joint deadline is that it was developed through the international collaboration with the regional groups. Experts from the CSCO and ASCO shared interpretation of the evidence while accounting for the organizing national or cultural diversity of different regions. In brief, the guideline provides the guidelines on how to plan radiotherapy and when and how to add chemotherapy. Through the interpretation protecting the guideline, care providers can avoid over or under-treatment. And providing the most suitable chemoradiotherapy for NPC patients.

Besides, for the patients, they could receive the most suitable treatment, which is the balance of the efficiency as a quantity of the life. Thank you.

BRITTANY HARVEY: Great. Definitely, we appreciate the collaboration between the American Society of Clinical Oncology and the Chinese Society of Clinical Oncology. So thank you so much for your work on these guidelines. And thank you for your time today, Dr. Ma.

JUN MA: Thank you.

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/head-neck-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.

Systemic Therapy for Advanced Hepatocellular Carcinoma Guideline Nov 16, 2020

Show notes

An interview with Dr. John D. Gordan from the University of California, San Francisco, and Dr. Michal G. Rose from Yale Cancer Center and VA Connecticut Healthcare System on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline." This guideline addresses first-line and subsequent systemic therapy options for patients with unresectable hepatocellular carcinoma that is not amenable to local therapies. Read the full guideline at www.asco.org/gastrointestinal-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 podcast.asco.org

My name is Brittany Harvey, and today I'm interviewing Dr. John D. Gordon from the University of California, San Francisco, and Dr. Michal G. Rose from Yale Cancer Center, and VA Connecticut Health Care System, co-chairs on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline." Thank you for being here Dr. Gordon and Dr. Rose.

DR. MICHAL G. ROSE: Thank you.

DR. JOHN D. GORDON: Thank you.

DR. JOHN D. GORDON: I do not.

BRITTANY HARVEY: Thank you. And Dr. Rose, do you have any relevant disclosures that are related to this guideline topic?

DR. MICHAL G. ROSE: I do not, either.

BRITTANY HARVEY: OK, then thank you. Then Dr. Rose, can you first explain the general purpose and the scope of this guideline?

DR. MICHAL G. ROSE: Of course. Thank you for this opportunity. As people know, the incidence of liver cancer, hepatocellular carcinoma, is rising rapidly in the United States and worldwide. And although there are multiple local and potentially curable treatments for early stage disease, the medical oncologist does get involved when these fail or if the patient presents with metastatic disease. And over the last three years, or bit more than three years, we've gone from having only one agent for advanced disease, which is sorafenib, to having nine agents approved for either first or subsequent lines of treatment. So this has created a really good problem for medical oncologists, how to choose between these multiple options. So the purpose of our guideline is to help us select the best treatment for the individual patient based on the best current evidence.

BRITTANY HARVEY: Great. Then this guideline covers both first line and subsequent systemic therapy options for patients with advanced hepatocellular carcinoma. Dr. Gordon, what are the key recommendations for first line therapy?

DR. JOHN D. GORDON: Thanks, and it's also a great pleasure for me to be on this podcast and I appreciate the entire process of putting together this guideline. In the front line setting, a lot of what motivates the completion of this guideline is the approval of the first front line combination for advanced HCC, which is the combination of bevacizumab and atezolizumab. So this was approved based on a report in the New England Journal of Medicine back in May that specifically studied a first line population of patients with advanced HCC and relatively preserved liver function. And the key recommendation of this guideline is that the combination of atezolizumab and bevacizumab be adopted for patients that meet this description. Particular caution is recommended for patients who are at risk of specific side effects or adverse events with these agents.

So for patients receiving bevacizumab, there is a particular risk of bleeding complications and MI or other ischemic complications. And so for patients with a recent MI or with uncontrolled esophageal varices, we recommend either management of these or not using this combination. Similarly, there are a range of contraindications to use of PD1, PDL1 inhibitors, such as atezolizumab, including history of various autoimmune diseases. And so we do not recommend this combination for patients with those co-morbidities. For patients with either more advanced liver failure or the specific risks that I just outlined, we're recommending continuation when safe and appropriate, of what was the previous standard of care. Which is front line treatment with either the oral TKI lenvatinib or the oral TKI sorafenib.

BRITTANY HARVEY: Great. Thank you for that overview of the first line recommendations. And Dr. Rose, what are the recommendations for second line therapy?

DR. MICHAL G. ROSE: So our team had a harder time with second line recommendations. And mainly because there's a lack, currently, of published data on treatment outcomes in patients who've received atezolizumab plus bevacizumab front line or lenvatinib front line. So we debated a lot in our group, which was a very multidisciplinary and collaborative group. And we did agree that patients who are well enough to receive second line therapy, that is their Child-Pugh was still A, and they had a good performance status, they should be considered for sorafenib, oral lenvatinib, if they had received atezolizumab plus bevacizumab in the front line setting. But of course other options for the second line would be cabozantinib or regorafinib, are reasonable in the evidence based options.

In patients who received sorafenib oral lenvatinib front line, we also discussed that it was reasonable to treat them with atezo bev because we presume that these patients did not have access to that combination in the front line. Of course if they meet the criteria that John outlined in the discussion of front line treatment. In patients who received sorafenib or lenvatinib front line, of course that we have data on using other tyrosine kinase inhibitors, such as cabozantinib or regorafinib. We also have data on using ramucirumab in patients who have an alpha fetoprotein greater than 400. And those were the recommendations that we made.

The other discussion that we had in these guidelines was the use of the immune checkpoint inhibitors second line. And we made the recommendation that they should be considered for patients who received sorafenib or lenvatinib in the front line setting, especially if they have contraindications to the use of further tyrosine kinase inhibitors. Or if they could not tolerate tyrosine kinase inhibitors.

BRITTANY HARVEY: Got it. Thank you for reviewing those second line systemic therapy options. Then Dr. Gordon finally, what is the importance of this guideline and how will it impact clinical practice and affect patients with advanced hepatocellular carcinoma?

DR. JOHN D. GORDON: Thanks. And so I think this very much follows on Michal's initial introduction about the purpose of this guideline, which was to address the dramatic proliferation of approved agents for advanced HCC. And what we were attempting to do, and I think achieved to the best that the evidence would support, was provide some degree of guidance on how providers could select both their first line agent and then later lines of therapy to the extent that patients are able to receive it. We think that the availability of these multiple agents for HCC, as Michal alluded to, is really an embarrassment of riches and now we need to think about how to use them wisely.

And we hope that actually as these new combinations and just a greater set of options enter clinical practice, it will be possible to actually do some of the studies that would address the questions that right now remain unanswered around treatments sequencing and the like. I think that there remain some interesting questions in the management of HCC, both for patients with more impaired liver function and for patients at the threshold between localized HCC who are still candidates for local regional therapies such as TACE or selective internal radiotherapy, and requiring systemic therapy as the outcomes from systemic therapy are becoming more positive. But in aggregate we think that these guidelines now provide something of a sequence for the treatment of patients who do require systemic therapy and hopefully an outline for further development.

BRITTANY HARVEY: Great. Thanks. It sounds like this will be important for both practitioners, and patients. So I want to thank you both for joining me on the podcast today and for your leadership on the development of these guidelines, Dr. Rose and Dr. Gordon.

DR. MICHAL G. ROSE: Thank you. And thank you for the opportunity to discuss them.

DR. JOHN D. GORDON: Yeah, thanks as well. And thanks to the amazing team at ASCO and to the entire expert panel, which put in quite a bit of time over the several years that we developed this guideline as more and more data became available.

BRITTANY HARVEY: Great. 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/gastrointestinal-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've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer Guideline Update Oct 20, 2020

Show notes

An interview with Dr. Neelima Denduluri from Virginia Cancer Specialists, U.S. Oncology in Arlington, VA and Dr. Sharon Giordano from the University of Texas MD Anderson Cancer Center in Houston, TX on "Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update." This update addresses the use of adjuvant trastuzumab emtansine and the use of biosimilar forms of trastuzumab. 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 podcast.asco.org. My name is Brittany Harvey, and today I'm interviewing Dr. Neelima Denduluri from Virginia Cancer Specialists, US Oncology in Arlington, Virginia, and Dr. Sharon Giordano from the University of Texas M.D. Anderson Cancer Center in Houston, Texas, co-chairs on "Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update."

Thank you for being here, Dr. Denduluri and Dr. Giordano.

Dr. Neelima Denduluri: Thanks for having us.

Dr. Sharon Giordano: Yeah, we're delighted to be here. 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. Denduluri, do you have any relevant disclosures that are related to this guideline topic?

Dr. Neelima Denduluri: Our institution has received research funding from companies including Genentech.

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

Dr. Sharon Giordano: No, I don't have any relevant disclosures. Thank you.

Brittany Harvey: Thank you. Then let's get into the guideline content. Dr. Denduluri, what prompted this focused update of the selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer guideline?

Dr. Neelima Denduluri: There was an FDA meta analysis and several other studies that showed that patients that did not receive a pathologic complete response after preoperative therapy in the HER2-positive setting had a worse prognosis. In the past, we didn't have actionable findings to improve their outcome.

But there was a trial, the KATHERINE trial, that randomized patients that received chemotherapy and trastuzumab, plus or minus pertuzumab, that did not achieve a pathologic complete response to receive standard of care trastuzumab or 14 cycles of trastuzumab emtansine. And the patients that received trastuzumab emtansine had a significantly improved outcome over those that received standard of care trastuzumab. These were very impactful findings that changed care for women with early breast cancer. Therefore, we wanted to update the guideline.

Brittany Harvey: So Dr. Giordano, there are two new recommendations in this guideline update. First, what does the guideline say regarding the use of adjuvant trastuzumab emtansine following standard preoperative chemotherapy and HER2-targeted therapy for patients with HER2-positive breast cancer with residual invasive cancer in the breast or lymph nodes at surgery?

Dr. Sharon Giordano: So the first recommendation was based on the data from the KATHERINE trial that Dr. Denduluri just mentioned. And so their recommendation is that patients with HER2-positive breast cancer who have pathologic invasive residual disease at surgery to either in the breast or the lymph node after standard pre-op chemo with HER2-targeted therapy should be offered 14 cycles of adjuvant trastuzumab emtansine unless there's a recurrence or unworkable toxicity. So basically stating, based on the data from KATHERINE, that if patients have residual disease after their chemotherapy for HER2-positive breast cancer, they should get adjuvant trastuzumab emtansine. And the panel overall felt that the evidence behind this-- the quality of the evidence was very high, and it had a strong recommendation for this treatment.

Brittany Harvey: And then second, Dr. Denduluri, how does this guideline address the use of biosimilar forms of trastuzumab?

Dr. Neelima Denduluri: So biosimilars are increasingly being incorporated into clinical practice, and the guidance that we have from the FDA is that the efficacy of biosimilars compares well with standard trastuzumab. So, we said that patients that would receive trastuzumab are allowed to receive trastuzumab biosimilar without what we think will negatively impact their outcome.

Dr. Sharon Giordano: For that recommendation, we also had input from the Breast Cancer Guideline Advisory Group that helped us decide to expand the update to include the biosimilars. We think that at least five biosimilars have been approved by the FDA, and based on similar efficacy and similar safety data felt that it was appropriate to use them or trastuzumab in a setting where previously we had just used trastuzumab.

Brittany Harvey: Great. And then how will this guideline update impact clinical practice?

Dr. Sharon Giordano: I think that many practitioners have already adapted clinical practice to start to use adjuvant trastuzumab emtansine based on the KATHERINE data, but we certainly hope that this guideline update will reinforce the practice of providing adjuvant trastuzumab emtansine for patients with HER2-positive breast cancer with residual disease after preoperative treatment. The improvement in outcomes was really clinically meaningful for patients, so this does seem to be a significant step forward in the treatment of HER2-positive breast cancer.

Dr. Neelima Denduluri: Additionally, I think that it's important to remember, as clinicians, that we should think about preoperative therapy in those patients with higher-risk HER2-positive disease, because we know that we can impact their outcomes if they don't achieve a pathologic complete response. And hopefully this guideline will heighten the awareness that we need to do that. The other question that we commonly are asked is, even if there is a small amount of residual invasive carcinoma, should we switch to trastuzumab emtansine instead of trastuzumab plus or minus pertuzumab. And what the KATHERINE data did show is that patients that-- even if they had a small amount of residual cancer burden, they still derived benefit.

Obviously, we have to think about the safety, and we also wanted to outline that in this guideline that trastuzumab emtansine is associated with a higher risk of neuropathy and thrombocytopenia and liver function abnormalities. So we certainly need to worry about that. And those patients that do have poor tolerance, we can go back to their HER2-targeted backbone they received in the preoperative setting.

Dr. Sharon Giordano: Yeah, those are great additional points.

Brittany Harvey: Definitely. And you've both already touched on a bit of how adjuvant therapy impacts patients, but how will these guideline recommendations affect patients?

Dr. Neelima Denduluri: I think that really, as Dr. Giordano stated, this is an overwhelming benefit that we don't normally see in terms of impacting outcomes. So the addition of trastuzumab emtansine potentially has good efficacy for them and improves their outcomes.

Dr. Sharon Giordano: Yeah, I agree. I think this trial was associated with a really meaningful reduction in risk of recurrence and better outcomes. So this really is a step forward for treating HER2-positive breast cancer.

Dr. Neelima Denduluri: The other interesting thing about this trial is that it did not delay their local therapy. They allowed concurrent trastuzumab emtansine with radiation therapy. And they also, in terms of systemic therapy, allowed endocrine therapy with trastuzumab emtansine, similar to what we do with trastuzumab plus or minus pertuzumab in the adjuvant setting. So as Dr. Giordano stated, really impactful in terms of efficacy, well-tolerated in most situations, and pragmatic in terms of not holding up the local therapy and the systemic therapy that they may need additionally.

Brittany Harvey: Great, thank you so much for sharing that information about how it impacts patients. I appreciate you both coming on the podcast today and for all your work that you put into updating these guidelines. And thank you for your time today Dr. Giordano and Dr. Denduluri.

Dr. Sharon Giordano: Thank you so much. It was a pleasure.

Dr. Neelima Denduluri: Thank you both, and thank you Brittany for always working so hard to make sure that these guidelines help our patients.

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/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.

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