Dr. Zofia Piotrowska: So maybe with that, let's talk a little bit about how we select systemic therapy for these patients. I think first maybe let's talk- Nick, you're seeing this patient after surgery. So, we're following the patient journey. The patient's had a resection and they're coming to you now. And so, how do you talk about- with them about adjuvant therapy? And I think this is probably a point too to talk about the role of both chemotherapy and the TKI, which we've already started to touch on.

Dr. Nicholas Rohs: Absolutely. So, as you- as you alluded to, this is a journey the patient is going on and they start with an interventionalist getting a biopsy. And I love the fact that Gus was talking about setting the stage. Because I think that's so important. Setting appropriate expectations for the patient. Because as they go throughout their journey, you're going to have new pieces of information for them to digest. And then making sure that we get quick testing done is really important. But we all live in a very lucky world where we have often reflexive in-house testing and really fancy panels we're running at our large academic institutions. But that's not often the case for a lot of people in the community and throughout the world. So, this is really a challenge, and we have to continue to advocate for getting these biomarker tests quickly and efficiently done for our patients because sometimes they show up at my door without this information. And that's the most challenging situation for me. How do I inform you if I don't have this information? But in a perfect world, if I do, then I can have a really good, informed discussion with my patient. You've had your treatment for your- with surgery, this tumor is removed, and I hope we are sitting in a cancer-free room right now where you are cured of cancer. But there is a real chance that the disease is going to come back, and we have a couple of options in front of us. And if I have that biomarker testing, I can think about immunotherapy, I can think about chemotherapy, and I can think about targeted therapy with Osimertinib. And that allows me to pick the right pathway for the patient. So, since we're focusing on eGFR, I'll talk about that some more. We're all excited about this data. This is amazing. This is great. And I think a lot of us are going to adopt Osimertinib adjuvant for these patients. But we can't forget chemotherapy. Chemotherapy is so critical for these patients because it is now these- one of the two things that are improving overall survival, but it does improve overall survival. So, we don't want to just say, oh, let's just go with the pill and forget about the chemotherapy. So, you have to think about the patient in front of you. They've been through surgery, they're still recovering, so nobody feels like rushing to chemotherapy. But we do know that that's an important thing for our patients to do. So, we have to select the right patient and make sure they have the right organ function, the hematologic function, and that's in line with their goals of care. So, you have that risk-benefit. Because on average, we're adding about a 5% reduction of recurrence risk with chemotherapy. But that's a real number and we have that discussion. And then I have a secondary discussion, or I guess kind of a co-mingled discussion these days of- And then if you have this eGFR mutation, you have Osimertinib available to you. And as we talked about before, depending on the stage, the benefit can go up in grade. But that for most patients, 1B through 3A, this is going to be benefiting you, letting you live longer and hopefully better. And I think that's the really important discussion we have. And then, of course, we can think about some other novel therapies like postoperative radiation therapy, but those are falling out of favor pretty quickly. Especially based off of the Lung ART trial that showed that it did improve local control, but not necessarily survival, given the cardiotoxic effects of the radiation. So, it's becoming a really hard conversation, but I always remember at the end of that conversation is a patient who has a life to live, and I want to make sure that we're making the right decision for that patient in front of me.

Dr. Zofia Piotrowska: Absolutely. I think it's really important to drill down on this question about chemotherapy a little bit more. This was a big topic of discussion around ADUARA, and I think continues to be. So, I want to kind of pull our other medical oncologist. How do you view the role of chemotherapy? Is it different at all in the light of ADUARA or do you view those as separate decisions?

Dr. Lyudmila Bazhenova: I think it's a separate decision. I think ADUARA did not prove to us that we can stop giving adjuvant chemotherapy. That was not the question that was designed to be answered by ADUARA. As Nick said, this is a proven way to increase the cure rate of early-stage lung cancer. Yes, the number is small, but there is a number. And I think until you tell me that you run a randomized study where you compare eGFR- patients with eGFR mutations who are randomized to chemotherapy followed by Osimertinib versus Osimertinib, I will continue to offer chemotherapy to my patients.

Dr. Zofia Piotrowska: Ashish, what do you think about it?

Dr. Ashish Saxena: I think I totally agree. I think the study didn't answer that question. It wasn't meant to answer the question of whether you need chemotherapy or not. The patients that got or didn't get chemotherapy were based on their own preferences and decision. It wasn't a randomization. It wasn't anything controlled. So, I don't think we can say that chemotherapy is not needed. And I think we would- I would continue to use it the way I was using it even before ADUARA. It's adjuvant, you have stage two, stage three lung cancer. I know, as Nick and Luda said that there's data that the chemotherapy is going to improve your overall survival.


Dr. Nicholas Rohs: And I think if we look at the appendix that actually the chemotherapy- patients who receive chemotherapy, there is a trend towards better survival. So, we can't forget about the importance of this.

Dr. Zofia Piotrowska: I totally agree, and I hope that maybe in the future we will have that study, Luda. I think it would be such an incredibly important study. In the past, we've had kind of either-or studies largely done with older first and second-generation eGFR inhibitors randomized against chemotherapy done in Japan and China. And we didn't see an improvement in survival there. But I think it's a different question now in the setting of Osimertinib. And so, perhaps we'll have more information. But for now, I agree. I think these are two separate conversations that you need to have with these patients. And these decisions have to be made independently of one another.

Dr. Jay Moon Lee: If I could just add to that, as a surgeon, I always get- I am- I'm the immediate second opinion. As soon as the patient sees the medical oncologist, should I get the chemo? And what I tell my patients when they ask me this question with the issue of chemo or not in ADUARA, if you look- Yes, it is true that 40% of the patients didn't get chemo in ADUARA, but when you look at it by stage, stage 1B, 85% didn't get it. When you look at stage two, 30% didn't get it. And when you look at stage three, 19% didn't get it. Medical oncologists feel that you follow the indications for chemo separate from the issue of OSI. And the higher the stage, the patients are more likely to receive it. So, I think it's more stage dependent rather than a yes-no binary issue of yes or no chemo. I think it's still dependent on how you would deliver chemo or recommend it, which is stage directed.


Dr. Nicholas Rohs: Absolutely. I don't think this should change the discussion we used to have about chemotherapy, about the stratification of risk benefits. So that's a really important point.

Videos

On the subject of patient eligibility, the panel deliberates on the decision-making process between osimertinib and chemotherapy and outlines adjuvant therapy options.

Selecting Appropriate Adjuvant Therapy for Patients with EGFR-Mutant NSCLC

Dr. Zofia Piotrowska: We're all adopters. Clearly, we've all drunk the Kool-Aid and I think are going to be continuing to offer this to our patients, but it really emphasizes the point of testing, and how critical testing is to these patients in the early-stage setting. And Gus, maybe as an interventional pulmonologist, I can bring you in because you're often the first point of contact for some of these patients. They may come in with a lung-screening CT, they may come in for a bronchoscopy, and so you're meeting them. What do you think about testing on that initial sample? Are you ordering it? Is it something that you're deferring to colleagues? And if so, what testing do you think should be done?

Dr. Gustavo Cumbo-Nacheli: Thank you for that question. The success of the treatment plan is directly proportional to the amount of time and conversation we have with the patient the first time we shake their hands. This is a high-level discussion with experts, and all of you provide treatment, whereas, maybe, the surgeon and I, we do the pre-treatment, which is diagnostic. The patient doesn't know when shows up in the clinic, what's going on, and what's going to happen. They don't know anything about personalized medicine or nodule risk gratification. So, at the very beginning, we have to prepare the patient that the biopsy is going to put a first name into the tumor they have, then there's testing that is going to put the last name. There's going to be waiting time in order to know what a preoperative treatment will be, and even if they were to have surgery, there may be other treatments that may happen before and after. So, communication with the patient is very important to secure the success of a program, and also, we discuss, well, there may be some testing that may happen after the initial biopsies. There are twice that we are going to have the opportunity of checking if there are any type of genetic rearrangements or DNA abnormalities that would allow for you to get a specific treatment that will be helpful for you. And obviously, we set the stage for them to go in-depth with discussions about different treatment options, and then, hopefully, they will be able to explain what true value care is provided to them, which is a good quality medication, better outcomes, and lower cost overall. So, we are openers for them to be closers, if you will, but it's very important that the first point of contact after a positive-screening CT, after a pre-resection, the pulmonologist or the interventional pulmonologist discusses that testing is coming. It may take a little while, but please, give us the time to get the chest set right in order for us to move forward.

Dr. Zofia Piotrowska: Such an important point, especially critical in that early-stage disease where patients are so eager to get to that next step. And Jay, you're often the next step in that journey for the patients as a thoracic surgeon. So, what testing are you checking to see? And maybe, specifically, what tests do you think need to be done here? Are you checking to see if they've been done on the biopsy? Are you ordering them on the resection specimen? So every institution, and geographically, everyone has a different workflow. What we do, at UCLA is to do reflexive NGS testing from the biopsy specimen. And often at the time of biopsy, we don't know what stage the patient has of- What stage of the non-small cell lung cancer the patient may have. So, the NGS testing has relevance, particularly, if the institution has clinical trials tied to targeted therapies in the early-stage setting. It has relevance in terms of efficacy or lack of efficacy with IO in the early-stage setting. And finally, to figure out which patients should go on ADAURA trial regimen, or which is now standard of care. So, the testing is critically important. I think there are two different sets of testing. One is the comprehensive NGS testing, both DNA and RNA. The other is, you want a quick turnaround on the PD-L1, the ALK, and the eGFR status. And they're mainly driven by IHC, but there are limited panels where you can get a quick turnaround on eGFR. So, right now we're in this kind of divisive situation where we're doing both NGS testing that takes a couple weeks, and then the quick turnaround test that we need to act upon right away.

Dr. Ashish Saxena: Oh, I was going to say- I think what Jay's saying is true, especially about the quick-turnaround times because we do have that other option of neoadjuvant chemoimmunotherapy, but it's not really for patients that have the eGFR or ALK mutation. So, getting that information sooner rather than later so we know what to do with them is really important.

Dr. Zofia Piotrowska: It's such an important point, and I think it is really important to keep in mind that in CheckMate816, the patients with eGFR and ALK alterations were excluded from that study. And even though we are starting to see now more studies where that, maybe, wasn't necessarily the case, I think we would all agree that if we have a patient that has a known eGFR mutation, chemo IO is not the right neoadjuvant therapy for them. And we can talk about, whether is there a right neoadjuvant therapy for them or should it be adjuvant. But I think what is clear right now is that those patients should not go on chemoimmunotherapy. And you can only make that decision if you do the testing. And so, I totally agree. I think getting that done right away is so very important.

Recommendations for community oncologists concerning molecular testing, including the types of tests, timing best practices, and how the results should inform treatment decisions.

Routine Molecular Testing in Early NSCLC Post-Resection

Dr. Zofia Piotrowska: I think it was with great enthusiasm that we were all awaiting the plenary session at this year's ASCO to see those overall survival results. And indeed we did, we did see Dr. Herbst present the updated results from the ADAURA data, including the overall survival analysis at this year's ASCO 2023. And what we saw is that indeed it was positive for overall survival. So, the median follow-up was 62 months in the osimertinib arm and 60 months in the placebo arm, and we saw that, for the primary-study population of stage-2-to-3a disease, the overall survival hazard ratio was 0.49. So, if we look at the landmark, five-year survival, it was improved from 73% in the placebo arm to 85% in the osimertinib arm. And the results in the overall study population bringing in those stage 1b patients were actually very, very similar. The hazard ratio there, again, was 0.49, and the improvement was from 78 to 88 percent. We saw that when we looked across subgroups, that benefit was maintained, really, across subgroups. When we looked by stage breakdown, as we had seen with the DFS, I think, the magnitude of benefit was higher in the higher-stage patients, which we would expect, and in the stage-3a patients, the OS hazard ratio was 0.37. So, really emphasizing the benefit for them. I think that, really, the benefit was maintained, again, across different subgroups, across eGFR mutations although, as we've seen in the metastatic setting, the exon 19 patients tended to do a little bit better. And importantly, and we'll come back to this, we saw that benefit was maintained whether or not patients received adjuvant chemotherapy, which as per the investigator's choice. In the study. There was a little bit of data, although I think it would be interesting to see more about the post-treatment outcomes and the therapies that patients were able to access. We did see that more patients access osimertinib in the placebo arm than in the osimertinib arm, but I think we need to see a lot more granularity to really understand the impact and to see what access looked like for those patients. But overall, I think there was a lot of enthusiasm. And so, maybe I'll ask the same question of everyone on the panel say what was your take on that overall survival data, and did it change your perspective? What do you think was the key take homes? What are you going to talk to about your patients when you see them in the clinic next week with this data in hand? Lyuda, maybe I'll start again with you.

Dr. Lyudmila Bazhenova: I think it undeniably improves overall survival. I think the data is very strong. The absolute benefit is more than 10%. What I think we don't know yet is if we are curing the patients. But in my opinion, the goal of the oncologist is one. Our major goal is to make our people live longer. So, at this point, I was an adopter and it just reinforced what I do, but when I'm explaining to the patients, I don't think we can use the word 'cure' yet, because those patients with eGFR mutations tend to recur later, and so, maybe five years is not enough, but it’s clearly making our patients live longer, and that's- I think the most important factor.

Dr. Zofia Piotrowska: And Benjamin Bessie, I think did a beautiful job of kind of summarizing and making that point and saying we need more time and more follow-up to really know," but it certainly seems to improve outcomes, and there's essentially about 10% of patients that wouldn't have been alive if they hadn't received that osimertinib. So, it was really great. Nick, how about you?


Dr. Nicholas Rohs: I think, definitely, we've reaffirmed that it makes people live longer. It's practice reaffirming what we're doing right now, at least what I was doing in my clinic, but I harbor the same concerns that you have, is this truly curing people? But again, we talked about that's not- We want to have people live longer, we also want them to live better. And I think that most people are living better. I do think that Dr. Bessie did a great job of also highlighting the fact that Tagrisso or osimertinib is not fully benign as far as the side effect profile. So, we do have to take that into account, but I think that this is making people live longer. And as we see the pace of eGFR treatment going at light speed right now, who knows what we're going to have five years from now on a patient who goes on adjuvant osimertinib. So, I think that that's absolutely a valuable time point to get them to.

Dr. Jay Moon Lee: I would just add to it that ADAURA really put the stamp of sealed that DFS is a surrogate for OS for a TKI in the early-stage setting. To me, that was very meaningful and significant from the ASCO presentation with ADAURA OS data. And then secondly, when you look at the time of relapse amongst patients, what's the next therapy that those patients went onto? And the highest percentage 41% went on eGFR TKI, which alludes to everything that my colleagues are saying that patients probably need to be on it longer. And then the other finding that I found interesting is that the second drug that patients most likely went onto was other TKIs, suggesting resistance mechanisms. So, this really leads to the future of, we need combination-targeted therapies in the early-stage setting, a more personalized approach in the importance of testing to figure out the resistance pathways and combination approaches, just as we're doing in the late-stage setting, but we need to bring that to the early-stage setting.


Dr. Zofia Piotrowska: Such an important point. I absolutely agree.

Analyzing a recent overall survival analysis from the ADAURA trial, its impact on practice, and changes in the treatment landscape of early NSCLC.

Latest Overall Survival Analyses in Resected EGFR-Mutated NSCLC

Dr. Zofia Piotrowska: To frame this conversation about early-stage disease, we really have to start by talking about the ADAURA study. And so, Ashish, we heard about ADAURA first in 2020 in the plenary session of that virtual ASCO, and maybe, let's start by actually just diving right into the ADAURA data. Can you tell us a little bit more about that study?


Dr. Ashish Saxena: Yeah, so, the ADAURA trial was a phase three, double-blind, randomized-control study of patients with surgically resected stage 1b to 3a non-squamous non-small cell lung cancer whose tumors harbored actionable eGFR mutations, specifically, the exon 19 deletion mutation or the eGFR L858R mutation. Now, all of these patients, as they said, had to have had a complete resection. They were allowed to get adjuvant chemotherapy, which they did about 60% of the time, but it wasn't required. But regardless of that, they were randomized one-to-one to either get osimertinib at 80 milligrams daily for up to three years or a placebo. So, it was a placebo-controlled trial. The population was- I should start with the endpoints. The primary endpoint was disease-free survival in the group that was stage 2 to 3a, and then that was the primary endpoint. The secondary endpoint was disease-free survival in the total population as well as overall survival and safety. And the population was pretty much what you would expect in this group as we talked about, there was about 60% of the patients were Asian, 70%, roughly, were female, and 70% were never smokers. The age was a little bit on the younger side around the early 60s, and most of the patients, about 97% ended up getting a lobectomy. And so, the data itself was really encouraging and was positive in that the median disease-free survival was 66 months in the group that got osimertinib both in the group that was stage two to stage three A and the overall population. And that was compared to the placebo population had a median disease-free survival of about 22 months in the stage 2 to 3a population and about 28 months in the overall population. So, it was highly statistically significantly positive. The hazard ratio was 0.23 in the primary endpoint population from stage two to three A, and in the overall population, it was also high at 0.27. The patients had a higher chance of not having CNS progression, than the ones that got osimertinib. So, that was also an important endpoint with a really statistically significant high hazard ratio in that as well. In terms of safety, it had no new safety signals. It basically showed the toxicities that we're used to seeing paronychia, diarrhea, and dry skin. It was about a 3% ILD risk, and maybe, a 6% or so risk of cardiac events. There was maybe about a 13% dose reduction rate and a 12%- Or 12% dose reduction rate and 13% dose continuation rate. So again, pretty well tolerated, which is what we're used to seeing in the stage-4 setting. And even in the quality-of-life assessments, there was no difference in time to deterioration in those metrics.


Dr. Zofia Piotrowska: Thank you so much for that overview. It was really, I think, such an important study and really such a paradigm shift for us back in 2020 when this was presented. I remember thinking at the time that it was too bad, that it was the kind of peak of the pandemic, and we were all watching it from home and not being able to share it together because it was such an important moment. So, I'm curious, and maybe, Jay, for you and for all of us, as a- What was your take on ADAURA back then if we rewind a little bit to three years ago? Did you feel like the disease-free survival benefit was enough to change your practice and start referring patients to medical oncology to consider this or did you feel like you needed more data to convince you? And I'll ask the same question to the rest of our medical oncologists as well.

Dr. Jay Moon Lee: Well, first of all, ADAURA was a landmark study in that it really thrusts forward the role of targeted therapies in the resectable space. It is a landmark study and doing that, it introduced the concept of the need for biomarker testing, and molecular testing in the early-stage setting. So, with that respect, it's such an important study and a hallmark study. The hazard ratios for the DFS were so impressive, but the track record of TKS prior to that was that it was either neither significant in the DFS/EFS hazard ratios or it didn't get confirmed or validated in the OS data. So, there was skepticism about whether is this going to play out and be validated with the OS data. But for me, I think the DFS data was sufficient. The CNS efficacy with osimertinib and the superiority of that in preventing CNS events was, at minimum, a quality-of-life issue that improved that issue amongst patients in the resectable space. So, very meaningful study.

Dr. Nicholas Rohs: I'd say- I'd have to agree with Jay there, is that he touched on some really important points there. This is a landmark study. I think the DFS hazard ratio was striking to us. These are numbers that we're not used to seeing in lung cancer. And the CNS protection, because eGFR-mutated lung cancers love to go to the CNS to see that CNS protection is really important. But as you said also, DFS has not always translated into OS. So, I harbored some reservations, but this seems striking enough that I did start adopting it, at least for my stage 2bs and 3as, the more advanced patients. I was a little bit more reserved for my earlier-stage patients, but at that point, I thought it probably had enough importance, but we also will probably touch on this a little bit later, is that I also thought there is a subset of patients that don't deserve any sort of therapy. They're cured by their surgery. So, which is that subset that we shouldn't be treating with osimertinib? But given the dramatic benefit that seemed to be coming, it seemed like a really good conversation, and a conversation I had with my patients pretty much right after that data came out.


Dr. Zofia Piotrowska: I think such important points. Lyuda, what was your take?


Dr. Lyudmila Bazhenova: I agree with what you guys did. I think the decisions we make when we are treating patients with adjuvant therapy are done with the patient and not for the patient. So, when the first results of the other trial were presented when I was explaining the data to the patients, I would explain that we don't know if it increases survival. We don't know if it provides a higher cure rate, but what we know is that it will delay the recurrence. And the meaning of delay recurrence has a different feel for different patients. If we have a young patient, for them, delaying the recurrence means that they're not going to tell their kids that “my cancer's coming back,” and they don't have to put their life on hold, versus for some elderly person, 85, 90-year-old, maybe for them, delaying recurrence is not as important. So, I think it is- As for us as medical oncologists, it's important to make sure we translate the data of the study into a patient-understandable language and make a decision together with the patient.

Dr. Nicholas Rohs: And I'll say- Probably, the other thing is, my concern was what would happen after osimertinib? If that patient progresses after osimertinib, what's going to be the genetic landscape I'm dealing with? And I assume I've essentially used up osimertinib as a therapy, and if there isn't an overall survival benefit, did I use a really good therapy and not use it the right way? But again, I still wanted to adopt it pretty early on.


Dr. Ashish Saxena: I think it's always during the time we were worried about what's the overall survival going to be, but I think, as Nick said, we weren't used to seeing such impressive numbers. So, I think that's what made me also adopt it, and thinking the patient is here right now in front of me who has this resected cancer, who has an EDFR mutation, and am I going to withhold it and say, "Well, I just want to wait for more data," which is hard to do in the real-life setting?

Dr. Zofia Piotrowska: I am totally on the same page. I think, Lyuda, your point about individualizing these decisions for patients is so incredibly important, and it's not the same calculus for each patient, but I was actually surprised by the patients who came to me. I think they were also very much on board having read and kind of studied this. I think many patients were also really excited by this data. But of course, as we all alluded to, I think the elephant in the room was, what is the overall survival going to look like? Are we actually curing these patients or are we simply delaying the time to recurrence? Which I think is still an important factor, but clearly, what we are looking for in that adjuvant setting is the cure.

The panelists explore the groundbreaking ADAURA trial, covering its study design, efficacy and safety results, and the current clinical implications.

ADAURA Trial: Adjuvant Osimertinib and Clinical Implications

Dr. Zofia Piotrowska: Hello, and welcome to this OncLive Peer Exchange entitled eGFR Mutant Non-Small Cell Lung Cancer: Expert Perspectives in Testing and Targeted Therapy. I'm Dr. Zofia Piotrowska, and I'm joined today by a panel of experts in the field of lung cancer. I would like to welcome my esteemed fellow panelist to introduce themselves.

Dr. Lyudmila Bazhenova: Hi, I'm Dr. Lyuda Bazhenova, a thoracic medical oncologist from the University of California, San Diego.

Dr. Nicholas Rohs: Hi, I'm Nick Rohs from Mount Sinai Hospital in New York City.

Dr. Ashish Saxena: Hi, I'm Dr. Ashish Saxena from Weill Cornell Medicine, Meyer Cancer Center, also in New York City.

Dr. Jay Moon Lee: Hello, Jay Lee, UCLA Thoracic Surgery.

Dr. Gustavo Cumbo-Nacheli: I'm Gus Cumbo-Nacheli. I'm an interventional pulmonologist at Michigan State Corewell.

Dr. Zofia Piotrowska: Welcome everyone, and thank you so much for joining me today. Today we're going to discuss a number of updates in resectable and advanced non-small cell lung cancer. We'll discuss the data in the context of national guidelines, the treatment landscape, and most importantly, its impact on clinical practice. So, with that, let's get started with our first topic. So, we're going to talk first about resectable early-stage non-small cell lung cancer today. This year, we've seen a number of exciting developments and advances in early-stage disease, and I'm really excited to cover this topic. Lyuda, maybe we can ask you to start, and just give us a little bit of an overview of how you think about early-stage, stage one to three A, non-small cell lung cancer. And because today, one of our focuses is going to be on eGFR-mutant lung cancer, maybe a little bit also about what we know about the prevalence of eGFR mutations in this population.

Dr. Lyudmila Bazhenova: I think the first decision point we all have when we are dealing with patients with early-stage lung cancer is to determine if the patient is resectable or not. And that is determined generally not by us but by surgeons and many pieces of information go into that decision. Is the tumor resectable surgically? What's the whole situation? Does the patient have comorbidities that prevent him from having surgery? And then, once the surgery is performed, if surgery is appropriate, then that's where we come in as a medical oncologist because we need to make decisions on adjuvant therapy, and we need to know, do we do adjuvant therapy. What kind of adjuvant therapy are we going to do? And since our talk today is on the patients with eGFR mutation, I think it's important for us to know how often we see those patients. And your likelihood to have seen the patient depends on where you practice. So, if you practice in Asia, you're probably going to see a lot of Asian never-smoking females, and you're likelihood of finding any eGFR mutation would be probably around 50%. In the United States and in Europe, the incidence of eGFR mutations is much lower, usually about 10 to 20%.


Dr. Zofia Piotrowska: I think we used to think about, maybe, eGFR mutations as not as relevant for early-stage disease, that it was something that we really only thought about and acted upon an advanced disease. And I think that's really changed so dramatically in the past couple of years.

After a brief introduction, Lyudmila Bazhenova, MD reviews treatment options for early-stage NSCLC, the prevalence of EGFR mutations, and guidelines for managing patients with stage 1b resectable disease.

Treatment Options for Stage I-IIIA NSCLC

Zofia Piotrowska, MD, assistant professor of medicine, Harvard Medical School, assistant in medicine, Massachusetts General Hospital, discusses the management of paronychia associated with EGFR TKIs.

Although paronychia is an adverse effect (AE) commonly associated with all the class of EGFR TKIs, many patients do not recognize this as a treatment-related AE, Piotrowska says. Patients who experience paronychia may turn to a podiatrist or primary care physician, and an oncologist may be unaware of the AE as a result, Piotrowska explains. Educating patients about the possibility of paronychia as an AE associated with an EGFR TKI is important, she stresses.

When patients present with mild symptoms of paronychia, soaking nails with warm water and Epsom salt or topical steroids can be helpful, Piotrowska continues. If symptoms are ongoing and not improving, dose interruptions may be useful in the event of severe cases of paronychia, she adds. For patients with ongoing and recurrent paronychia, a referral to a dermatologist can also help them manage the AE, Piotrowska concludes.

Zofia Piotrowska, MD, discusses the management of paronychia associated with EGFR TKIs.


Dr. Piotrowska on the Management of Paronychia Associated With EGFR TKIs

Zofia Piotrowska, MD, MHS, a medical oncologist at Massachusetts General Hospital and an instructor at Harvard Medical School, discusses the utility of mobocertinib (formerly TAK-788) in patients with non–small cell lung cancer (NSCLC) who harbor 

Mobocertinib is an oral TKI that has demonstrated significant efficacy among patients with NSCLC and 

 exon 20 insertion mutations, says Piotrowska. During the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer, findings from a phase 1/2 study of mobocertinib in this patient population were presented and revealed an objective response rate of 26% per an independent review committee and 35% per investigator assessment. The median progression-free survival was 7.3 months. 

Although these results are encouraging, toxicity remains a concern with mobocertinib, as well as other emerging targeted therapies for this subset of patients, Piotrowska says. In the study, 90% of patients reported diarrhea and 45% reported rash as treatment-related adverse effects. Moreover, 21% of patients experienced grade 3 or higher diarrhea. As such, improvements in symptom management or development of novel therapies that are less toxic are needed, concludes Piotrowska. 

Zofia Piotrowska, MD, MHS, discusses the utility of mobocertinib in patients with non–small cell lung cancer who harbor EGFR exon 20 insertions.  



Dr. Piotrowska on the Utility of Mobocertinib in EGFR Exon 20–Mutant NSCLC 

Zofia Piotrowska, MD, MHS, a medical oncologist at Massachusetts General Hospital and an instructor at Harvard Medical School, discusses the patient populations eligible to receive osimertinib (Tagrisso) as treatment for lung cancer.

The results of the FLAURA trial led to Piotrowska giving frontline osimertinib to patients with 

 exon 19 deletion, L858R, and other sensitizing mutations. When the trial was first published, there was a debate regarding whether it was beneficial to give patients erlotinib or gefitinib upfront. If the patient developed a T790M mutation, that left osimertinib as an option for second-line therapy; however, only about 60% to 70% of patients will develop T7090M. On the other hand, if osimitertinib is given upfront, patients will benefit for ≥19 months. When using the mentality that the best drug should be given upfront, osimertinib should be the frontline treatment according to the FLAURA data, says Piotrowska.

Second-generation EGFR inhibitors are considered for patients with uncommon but still sensitizing EGFR mutations. Afatinib (Gilotrif) is the only FDA-approved therapy for those mutations currently. Data for using osimiertinib on patients with G719, S768I, and other mutations are still being developed, but osimertinib may be used for those patients, as well, concludes Piotrwoska.

Zofia Piotrowska, MD, MHS, discusses the patient populations eligible to receive osimertinib as treatment for lung cancer.

Dr. Piotrowska on Eligibility Criteria for Osimertinib in Lung Cancer Treatment

Zofia Piotrowska, MD, MHS, a medical oncologist at Massachusetts General Hospital and an instructor at Harvard Medical School, discusses treatment strategies for 

-mutant non—small cell lung cancer (NSCLC).

The randomized phase III FLAURA trial, which compared osimertinib (Tagrisso) with erlotinib (Tarceva) and gefitinib (Iressa), showed that osimertinib improved progression-free survival and overall survival compared with the first-generation EGFR drugs in patients with metastatic 

-mutant NSCLC. The FLAURA trial establishes osimertinib as a standard of care for newly diagnosed 

-mutant patients with NSCLC, according to Piotrowska.

Aside from monotherapy, some combination treatments have potential to become a standard of care, including the combination of EGFR inhibitors with VEGF-targeted therapies or with chemotherapy, says Piotrowska. Both of these strategies have shown promise when combined with first-generation EGFR inhibitors, according to Piotrowska, and upcoming trials will look at combinations with osimertinib.

Piotrowska says it is important to identify 

-mutant patients early because, even if they have high PD-L1 expression, EGFR inhibitors are the standard treatment. There is risk to starting immunotherapy prior to receiving the results of the 

 test, because immunotherapy is not an effective treatment for patients with this molecular driver. Additionally, the risks of an EGFR inhibitor can be increased if started after immunotherapy. Therefore, the results of the 

 test must be received before starting treatment to give 

-mutant patients the appropriate TKI, concludes Piotrowska.

Zofia Piotrowska, MD, MHS, discusses treatment strategies for EGFR-mutant non–small cell lung cancer.

Zofia Piotrowska, MD, MHS

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