Show notes
Doctors Vamsi Velcheti, Sandip Patel, and Michael Zervos discuss recent updates on the management of early-stage non-small cell lung cancer (NSCLC), including the optimization of neoadjuvant and adjuvant treatment options for patients and the role of surgery in the era of targeted therapy and immuno-oncology in lung cancer. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I am a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. On today's episode, we'll be discussing recent updates on the management of early-stage non-small cell lung cancer (NSCLC), including the optimization of neoadjuvant and adjuvant treatment options for our patients, and the evolving role of surgery in the era of targeted therapy and immuno-oncology in lung cancer. Today, I am delighted to be joined by two renowned experts in this space, Dr. Sandip Patel and Dr. Michael Zervos. Dr. Patel is a professor of medicine and a medical oncologist specializing in lung cancer at UCSD. Dr. Mike Zervos is the clinical chief of the Division of Robotic Thoracic Surgery and Director of General Thoracic Surgery at NYU Langone. Our full disclosures are available in the transcript of this episode, and disclosures relating to all episodes of the podcast are available at asco.org/DNpod. Dr. Patel and Dr. Zervos, it's a great honor to have you on the podcast today. Welcome aboard. Dr. Sandip Patel: Great to be joining you. Dr. Vamsi Velcheti: Let's get started with Dr. Patel. As you know, over the last decade we've had dramatic advances in systemic therapy options for patients with metastatic non-small cell lung cancer, in both the realms of targeted therapy and immunotherapy. These have significantly improved outcomes for our patients with metastatic lung cancer. What's exciting is that more recently, we've seen the incorporation of these agents, both targeted therapies and immunotherapies, in early-stage non-small cell lung cancer. Dr. Patel, can you tell our listeners about these exciting recent advances and why do you think it's so important to incorporate these personalized systemic therapy options for our early-stage patients? Dr. Sandip Patel: I think it's a great point and a great question. And so, I think one thing to understand is that non-small cell lung cancer is actually multiple diseases. We give it one name based on how it looks under the microscope, but the vast majority of our advances to improve outcomes for patients have come from our ability to understand specific subgroups. Many of our therapies have had activity in the advanced setting. We have our patients with metastatic or more widespread disease, which naturally led to the thought that could we utilize these therapies in earlier stage disease and potentially increase the rate of cure for many of our patients, lung cancer being the most common cancer killer worldwide. And so to your point, trying to understand how to best treat a patient really involves personalized medicine, typically driven by understanding the genomic profile of their tumor and two of the genes that have graduated from being tested for in the metastatic setting and now in the localized setting are EGFR and ALK. And these in particular are mutations that confer sensitivity to small molecule inhibitors, EGFR with osimertinib, ALK in the localized setting with alectinib based on the data that we've seen. And so, one of the areas that's been particularly exciting is our ability to maximize a patient's chance for durable remissions by integrating these therapies after surgery, after chemotherapy when appropriate, and continuing generally for a finite amount of time, two to three years depending on the agent in the study we're discussing for these patients. Additionally, immunotherapy, which has revolutionized our treatment of patients with metastatic disease, may be particularly well-suited for the localized setting of non-small cell lung cancer as well. Dr. Vamsi Velcheti: Excellent points, Sandip. You're absolutely right, in the metastatic setting, we've all come to accept molecular testing, sequencing, and biomarker profiling as a standard, but unfortunately, that hasn't quite yet percolated into the early-stage setting. Can you talk about some of the challenges that we face as we have these therapeutic options available now for more early-stage patients? Dr. Sandip Patel: So, I think there are 3 flavors of localized therapy in non-small cell lung cancer. One is the advanced, unresectable stage 3, for which the approach is often concurrent chemo-radiation followed by some form of consolidated therapy. We're about to hear the results of LAURA, which is the study looking at EGFR-mutated non-small cell lung cancer. For other patients, historically, the treatment has been durvalumab, an anti-PD-L1 directed immunotherapy. The other two are operative treatment of localized cancer: adjuvant treatment after surgery, or neoadjuvant or perioperative, in which chemoimmunotherapy begins before surgery. And testing depends on the settings. For the stage 3 patient who's likely getting concurrent chemo-radiation, they may have a very small amount of tissue, and so often these are done by pulmonary EBUS biopsies and that's how we pathologically confirm that advanced stage 3B. There may not be a lot of tissue available for molecular testing. In fact, if you look at the PACIFIC analysis, just looking at PD-L1, which is just an IHC off a single slide, a third of patients weren't able to even get a PD-L1, let alone a genomic result. And so, I think that's one of the areas of LAURA that's going to be particularly interesting to see as we try to implement it into our practice after seeing the full data. I think in the adjuvant setting, we're lucky because our surgeons, Dr. Mike Zervos here, will get us a large amount of tissue in the surgical resection specimen, so we tend to get enough tissue to do genomics while they're under chemotherapy, there tends to be time to wait for their genomic result. Where this really gets complicated is in the neoadjuvant or perioperative setting, where time is everything. The most important thing we can do for a patient in the localized space is get them to the operating room, get them started on radiation, their curative local modality, and that's where we have a time pressure but also a sample pressure because that is a diagnostic biopsy. It's a very small piece of tissue. Initially, there are multiple stains that have to be done to identify this lung cancer as opposed to another tumor. And so that's an area that I think we're going to need additional approaches given that cell-free DNA tends to have lower yield in lower stage disease in giving us a result. Dr. Vamsi Velcheti: Great points, Sandip. How do you deal with this issue in San Diego? The challenge is now we have a lot of trials, we'll talk about those neoadjuvant immunotherapy trials, but we know that immunotherapy may not be as effective in all patients, especially those with EGFR or ALK or some of these non-smoker, oncogene-driven tumors. So, we don't want to be giving patients treatments that may not necessarily be effective in the neoadjuvant space, especially when there is a time crunch, and we want to get them to surgery and all the complications that come with giving them targeted therapy post-IO with potential risk for adverse events. Dr. Sandip Patel: Absolutely. It is a great point. And so, the multidisciplinary team approach is key, and having a close relationship with the interventional pulmonary oncs, interventional radiology surgery, and radiation oncology to ensure that we get the best treatment for our patients. With the molecularly guided therapies, they are currently more on the adjuvant setting in terms of actually treating. But as you mentioned, when we're making a decision around neoadjuvant or perioperative chemo IO, it's actually the absence of EGFR now that we're looking for because our intervention at the current time is to give chemoimmunotherapy. Going back to the future, we used to use single gene EGFR within 24 hours, which was insufficient for a metastatic panel, but it often required five slides of tissue input. ALK can be done by IHC, and so some of these 'oldie but goodie' pathologic techniques, and that pathologists, if I haven't emphasized, understanding what we're trying to do at a different context is so key because they are the ones who really hold the result. In the neoadjuvant and perioperative setting, which many of us favor, especially for stage 3A and stage 2B disease, understanding how we can get that result so that we can get the patient to the operating room in an expeditious way is so important. There is a time pressure that we always had in the metastatic setting, but I think we feel much more acutely in the neoadjuvant and perioperative setting in my opinion. Dr. Vamsi Velcheti: Fascinating insights, Dr. Patel. Turning to Dr. Zervos, from a surgical perspective, there has been an evolution in terms of minimally invasive techniques, robotic approaches, and enhanced recovery protocols, significantly improving outcomes in our patients post-surgery. How do you see the role of surgery evolving, especially with the increasing complexity and efficacy of these systemic therapies? How do you envision the role of surgery in managing these early-stage patients, and what are the key considerations for surgeons in this new era? Dr. Michael Zervos: Thanks, Vamsi. Thanks, Sandip. Thank you for having me on the podcast. Obviously, it's an honor to be a part of such a high-level discussion. I have to say, from a surgeon's perspective, we often listen to you guys talk and realize that there's been a lot of change in this landscape. And I think the thing that I've seen is that the paradigm here has also changed. If we were having this discussion 10 years ago, a lot of the patients that I am operating on now, I would not be operating on. It really has been amazing. And I think the thing that stands out to me the most is how all of this has changed with neoadjuvant chemotherapy checkpoint inhibition. I think, for us as surgeons, that's really been the key. Whether it's CheckMate 816 or whatever you're following, like PACIFIC, the data supports this. And I think what we're seeing is that we're able to do the surgery, we're able to do it safely, and I think that the resectability rates are definitely high up there in the 90% range. And what we're seeing is pretty significant pathologic responses, which I think is really amazing to me. We're also seeing that this has now shifted over to the oligometastatic realm, and a lot of those patients are also being treated similarly and then getting surgery, which is something that we would not have even thought of ever. When you look at the trials, I think a lot of the surgery, up to this point, has been done more traditionally. There's a specific reason why that happens, specifically, more through thoracotomy, less with VATS, and less with robotic. Sandip, I think you guys have a pretty robust robotic program at UCSD, so I'm sure you're pretty used to seeing that. As you guys have become so much more sophisticated with the treatments, we have also had to modify what we do operatively to be able to step up to the plate and accept that challenge. But what we are seeing is yes, these treatments work, but the surgeries are slightly more complicated. And when I say slightly, I'm minimizing that a little bit. And what's complicated about it is that the treatment effect is that the chemo-immune check inhibition actually has a significant response to the tumor antigen, which is the tumor. So it's going to necrose it, it's going to fibrose it, and wherever there is a tumor, that response on the surgical baseline level is going to be significant. In other words, there are going to be lymph nodes that are stuck to the pulmonary artery, lymph nodes that are stuck to the airway, and we've had to modify our approaches to be able to address that. Now, fortunately, we've been able to innovate and use the existing technology to our advantage. Personally, I think robotics is the way we have progressed with all this, and we are doing these surgeries robotically, mainly because I think it is allowing us, not only to visualize things better, but to have sort of a better understanding of what we're looking at. And for that matter, we are able to do a better lymph node dissection, which is usually the key with a lot of these more complicated surgeries, and then really venturing out into more complicated things, like controlling the pulmonary artery. How do we address all this without having significant complications or injuries during the surgery? Getting these patients through after they've successfully completed their neoadjuvant treatment, getting them to surgery, doing the surgery successfully, and hopefully, with minimal to no morbidity, because at the end, they may be going on to further adjuvant treatment. All of these things I think are super important. I think although it has changed the landscape of how we think of things, it has made it slightly more complicated, but we are up for the challenge. I am definitely excited about all of this. Dr. Vamsi Velcheti: For some reason, like medical oncologists, we only get fixated on the drugs and how much better we're doing, but we don't really talk much about the advances in surgery and the advances in terms of outcomes, like post-op mortality has gone down significantly, especially in larger tertiary care centers. So, our way of thinking, traditionally, the whole intergroup trials, the whole paradigm of pneumonectomies being bad and bad outcomes overall, I think we can't judge and decide on current treatment standards based on surgical standards from decades ago. And I think that's really important to recognize. Dr. Michael Zervos: All of this stuff has really changed over the past 10 years, and I think technology has helped us evolve over time. And as the science has evolved for you with the clinical trials, the technology has evolved for us to be able to compensate for that and to be able to deal with that. The data is real for this. Personally, what I'm seeing is that the data is better for this than it was for the old intergroup trials. We're able to do the surgery in a better, more efficient, and safer way. The majority of these surgeries for this are not going to be pneumonectomies, they are going to be mostly lobectomies. I think that makes sense. I think for the surgeons who might be listening, it doesn't really matter how you're actually doing these operations. I think if you don't have a very extensive minimally invasive or robotic experience, doing the surgery as open is fine, as long as you're doing the surgery safely and doing it to the standard that you might expect with complete lymph node clearance, mediastinal lymph node clearance, and intrapulmonary lymph node clearance. Really, I think that's where we have to sort of drive home the point, really less about the actual approach, even though our bias is to do it robotically because we feel it's less morbidity for the patient. The patients will recover faster from the treatment and then be able to go on to the next phase treatments. Dr. Vamsi Velcheti: In some of the pre-operative trials, the neoadjuvant trials, there have been some concerns raised about 20% of patients not being able to make it to surgery after induction chemo immunotherapy. Can you comment on that, and w…
Full show notes at the publisher 
Our TOPPODCAST Picks 
Stay Connected
