What APs Need to Know About the Management of EGFR-mutated Metastatic NSCLC

Chaely Medley:

Welcome to JADPRO's Roundtable discussion on the management of EGFR-mutated metastatic non-small cell lung cancer. My name is Chaely Medley and I'm a thoracic oncology nurse practitioner at the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center. Joining me today are two of my colleagues: Beth and Whitney.

Chaely Medley:

Hi, my name is Beth Sandy. I am a nurse practitioner in the Abramson Cancer Center at the University of Pennsylvania.

Dr. Whitney Lewis:

My name is Dr. Whitney Lewis and I'm a clinical pharmacist at MD Anderson Cancer Center in the Thoracic and Head and Neck Medical Oncology Clinics in Houston, Texas.

Chaely Medley:

Beth and Whitney, thank you for joining me today. I thought we could start this Roundtable Series off by discussing the PAPILLON data, which offers a new standard-of-care frontline therapy for patients with advanced non-small cell lung cancer with EGFR exon 20 insertions. As background for this discussion, it's important to know that EGFR mutations are among the most frequent activating mutations in non-small cell lung cancer, and insertions in exon 20 represent up to 12% of all EGFR-mutated non-small cell lung cancers. Unfortunately, these cancers with exon 20 insertions are largely insensitive to TKIs that have been approved for the treatment of patients with common EGFR-mutated non-small cell lung cancer such as exon 19 deletion. And prior to this data, the standard of care for these patients was chemotherapy alone. PAPILLON is a phase 3 international randomized trial, which assessed the efficacy and safety of amivantamab plus chemotherapy compared with chemo alone as first-line therapy for patients with EGFR exon 20 insertion advanced non-small cell lung cancer. The use of ami-chemo in frontline therapy for these patients recently received FDA approval in March of this year.

Amivantamab is an EGFR mesenchymal-epithelial transition factor or MET bispecific antibody with immune cell-directing activity. It was previously approved in patients with EGFR exon 20 insertions, but only after progression, so that would be in the second-line setting. So, in the PAPILLON trial, there were 308 adults, and they were assigned to receive either IV amivantamab plus carboplatin and pemetrexed chemotherapy or carboplatin and pemetrexed chemo alone. And this would be in 21-day cycles, which is different than amivantamab in the second-line setting.

Patients assigned to chemotherapy alone could receive the amivantamab monotherapy after disease progression was documented. So, the primary outcome was progression-free survival, which was significantly longer at 11.4 months in the amivantamab chemotherapy group vs. 6.7 months in the chemo-alone group. Additionally, the ami-chemo group had an objective response rate of 73% vs. 47% in the chemo-alone group. And the overall survival favored the amivantamab group. In this study, 7% of patients receiving the amivantamab discontinued the drug for serious adverse reactions.

So Beth and Whitney, with this data, I wanted to discuss what this looks like in real life. I know that in my clinic we're using this but given that exon 20 insertions aren't as common as other EGFR mutations, we haven't seen a ton of this since it had received FDA approval. However, the patients that have been receiving it have been doing really well and tolerating the treatment very well. The most common adverse events in the amivantamab group with the published data were rash, nail toxicity, and infusion-related reactions. How are you guys seeing this implemented in your clinic and what are some of the side effects that you guys are seeing?

Beth Sandy:

Well, I'll start and just say, first of all, finding the exon 20 insertion, when we're reading these molecular pathology reports, we're so used to seeing the more common EGFR exon 19 deletion or 20 point mutation, also called L858R. So, it's really important for us as APPs when we're reading these molecular pathology reports to be able to identify that this is an EGFR exon 20 insertion. It will say that exactly on that molecular path report. And like you said, this is a lot less common in the overall population, but it's treated completely differently. Like you said, this does not respond to those typical EGFR TKIs that we use in the common mutations. I think that's the most important thing. Whitney, I'd be interested to hear from you about the infusion-related reactions and the administration time, and how you've managed that in your clinic.

Dr. Whitney Lewis:

Yeah, I think this was a really practice-changing publication. So, I would say, and I'm sure it's the same for you, Beth, we've definitely implemented this in clinical practice, but it does require a mindset shift for our patients as well as our physicians. I think, in lung cancer, we've been very spoiled because we've always had these every 3-week chemotherapy regimens. But when we start giving amivantamab, the very first dose is split up over 2 days and they're long infusion days, so 5 and 7 hours by the time you get all of the pre-medications in. And by the time you start stepping up that rate of the amivantamab, and hopefully, patients aren't having infusion reactions, but depending on the paper, anywhere from 50% to almost 70% of patients, despite what I would call pretty aggressive prophylaxis with acetaminophen and steroids and antihistamine are still having these reactions.

So, for the most part, for our patients, they've been pretty low grade, grade 1 or grade 2, but we have had a couple of more fragile patients who did require being admitted to the hospital and 1 or 2 that even had to be intubated for a few days because of a baseline tenuous respiratory status and infusion reaction didn't help that. So, the good news is, is that this reaction is pretty typical with only the first, maybe second dose. It's not a true anaphylactic reaction, doesn't require all these additional steps that we would do for desensitization with the platinums. We don't need to be aliquoting these bags. It just requires carrying on that steroid premedication. Is that typical for what you all have been seeing in your clinics with these patients?

Beth Sandy:

Yeah, it's generally something we'll pause, manage the reaction, but then we can re-challenge them, which of course then makes it a longer day. But like you said, once we get through those first couple doses, then generally, they do well in the future then. Chaely, how about you? What's the infusion-related reactions?

Chaely Medley:

That first cycle is pretty cumbersome with them having to come back every, like you said, Whitney, twice in the first week and then every other week after that for the full cycle. But then once we get into the second cycle and moving forward, then it's just every 21 days, which is most typical for a lot of our chemo cycles. And So, it's a little bit more tolerable in terms of time commitment for the patient. Maybe like financial toxicity when you're talking about traveling to the clinic and things like that, it falls into more of a regular routine after that.

Beth Sandy:

I think the other thing that we see a lot with amivantamab adding to chemotherapy is rash. And I know that this can be higher than 50% of patients developing that acneiform rash that we typically used to see with earlier-generation EGFR TKIs, not as much anymore with our third-generation agents. But with amivantamab, they brought the rash back. So, we do typically manage that. In my patients, if it's a mild rash, we'll just use a topical antibiotic like clindamycin gel, things like that, making sure they're moisturizing and using sunscreen. But a lot of these patients will require oral doxycycline and I'm pretty quick to go to that. It does tend to help the rash and really get it under good control. What have you guys noticed with rash and other skin toxicities?

Chaely Medley:

Certainly, pretty similar. I think most people get the rash, especially in the combination with pemetrexed. It seems like everything comes in waves, and right now, everybody's getting a pemetrexed-associated rash no matter what combination of medications you're using. And so, I'm also doing topicals, topical antibiotics, topical steroid creams, lots of emollient creams, avoiding things that might irritate the rash at all, lots of just teaching on supportive care with that. And then I too just will pretty much go straight to doxycycline or minocycline if patients are really struggling with the rash or if it's particularly bothersome. But especially in the summertime, it seems like people struggle with the rash more because they really want to go outside and be in the sun and we're advising them not to do that. And if you are, layer on the SPF, and the hats, and the long-sleeve UPF swimwear, things like that.

Dr. Whitney Lewis:

I think we have a very similar practice. We're pretty reactive with the rash management. We do spend a lot of time counseling patients, especially the male patients who tend to think of skincare as just splashing a little bit of water on the face. So, that can be a little bit of a culture change to be using moisturizers and cleansers and trying to give some good recommendations for gentle brands over the counter that don't break the bank. And So, we do spend quite a bit of time also talking about skincare and SPF because here in Texas, it's very intense sun and people do want to be outside as they're able to be.

And we also are pretty quick to put in a consult to dermatology. So, I think having that day 15 toxicity check in clinics sometimes toward the end of that first cycle with the chemotherapy, we may already be putting in a derm consult if things like the topical clindamycin, oral tetracyclines just aren't whacking that rash down as much as we'd like. And occasionally we'll also see the amivantamab rash in unusual places. So, that's been interesting to learn as well as we start implementing this in a wider patient population and in combination with chemotherapy. So, sometimes more on the trunk, or in the groin area, or under the axilla. We've also seen some unusual rash presentations.

Chaely Medley:

Another thing I want to bring up to you guys is the nail toxicity, which we do see a lot with EGFR inhibitors and commonly it's not something, having nail toxicity or the splitting of the nails, the paronychia, things like that are not things that we would really see with chemotherapy. And so I know with these patients I'm doing a lot of education on that. And So, what are ways that you guys are managing that and approaching that, preparing your patients for that type of side effect?

Beth Sandy:

I mean for me, with the feet, starting with feet, we would recommend, in the summer especially, that they wear open-toed shoes so that the feet are not tight inside of a shoe, especially if there's already inflammation around the nail bed. I mean paronychia is inflammation around the nail bed, so if you have something tight and enclosed around that, it's just going to make that worse. Now, in the winter, up north where I live, it gets cold, so not a lot of people are going to have their toes out all the time, but that's one way to prevent it. And just the obvious of keeping your nails clean, trimmed, not doing aggressive acrylic nail treatments and fake nails and things like that that are going to irritate the nail beds. But this can be really tricky. It can be really hard to get appropriate therapies to the actual nail beds. Whitney, have you had any luck with treatments?

Dr. Whitney Lewis:

We also will send our patients to a couple of dermatologists. Sometimes they actually need a little small surgical procedure. We're also pretty quick to tell them to start soaking their nails in a vinegar water solution or vinegar-bleach just to try to keep everything clean to try to prevent any infection from settling in there as well. And then conversely, on the other side, we'll sometimes see fissures in the nails. So, a lot of times we're asking our patients to sleep with gloves and Aquaphor just to try to keep everything moist and hydrated as well so they're not getting these cracks and fissures that can also cause infections. Or it sounds a little bit crazy but even a little bit of super glue sometimes can help smooth those cracks over and prevent any infections.

Chaely Medley:

That's pretty similar with my practice also. We've tried to encourage patients to use clobetasol cream around their nails if they need to. And sometimes that can be difficult for patients, especially when people work with their hands a lot and they're washing their hands a lot. They very much want to stick to the apply to the hands twice daily. But really, I'm encouraging them to just, if you wash it off, put it back on, it's okay to keep laying it on and keep your fingers covered. And we want that to heal because these are the types of things that can lead people to discontinue treatment because it can be very bothersome and interruptive to their ADLs.

The other thing that I wanted to mention is that in the PAPILLON study, serious adverse events occurred in 37% of the population and some of the most common were pneumonia, interstitial lung disease, PE, and pneumonitis. And So, it's important to mention that and broach the subject with the patients when you're doing your teaching because you want them to know what to be looking for and when it is something to call for and to be aware of. But we also don't want to alarm them in any way or make them any more nervous than probably is already happening with a diagnosis of advanced lung cancer. But this is something that's always a challenge I think in my lung cancer clinic is because patients already have respiratory symptoms and then these medications can exacerbate that and sorting through those things. So, do you guys have any tips for practitioners on how they might help sort through these adverse events and the presentations that patients might have when they come to clinic?

Beth Sandy:

I really think it's best that if they're short of breath, they call immediately so that we can work them up, diagnose them, get a CT of the chest, likely to rule out PE vs. pneumonitis vs. consolidation like pneumonia.

So, I also am excited about this possible subcutaneous administration. Whitney, what do you know about this? I think this is the PALOMA-3 trial that's ongoing, so it's not something that's approved yet, but we could be seeing a subcutaneous injectable form of amivantamab.

Dr. Whitney Lewis:

Yes, and I know it's not just us, but a lot of community centers as well are going to be very excited about a subcutaneous injection instead of these really long first few days getting infusions. I've heard from colleagues in the community that they might not even be able to really start a patient on amivantamab. They have to refer them for the first few weeks until it's down to a couple of hours of infusion just because their centers aren't open that late. So, I think this is going to be a really amazing product for patients. It also way cuts down on the rate of infusion reactions. I think it's somewhere in the 10% to 15% and almost all grade 1 or grade 2, so less likely and less intense reactions I think we're always a big fan of in terms of patient compliance, and then just getting this drug to patients who can actually access it and can really benefit from it.

Beth Sandy:

I'm excited to see that in the future.

Chaely Medley:

Me too.

Well, this brings us to the end of this discussion, and I want to thank my colleagues, Beth Sandy and Whitney Lewis, for taking time out of their busy days to talk with me. For more information and to view our other discussions on EGFR-mutated metastatic non-small cell lung cancer, please visit JADPRO online at jadpro.com. Thanks so much and have a great day.