Updates in Second-Line EGFR-Mutated Non–Small Cell Lung Cancer

Samantha Conlin:

Hello and welcome to JADPRO's roundtable discussion on Updates in Second-Line EGFR-Mutated Non–Small Cell Lung Cancer. My name is Samantha Conlin and joining me today are my colleagues, Mary Ellen Flanagan and Hailey Hunter. We are thoracic nurse practitioners at Washington University School of Medicine in St. Louis. And I'll let you guys introduce yourself.

Mary Ellen Flanagan:

I'm Mary Ellen Flanagan.

Hailey Hunter:

I'm Hailey Hunter.

Samantha Conlin:

And again, thank you both for joining me today. In the second installment of our video roundtable, we'll be discussing a case of a patient with EGFR-mutated non–small cell lung cancer receiving second-line standard of care therapy.

Hailey Hunter:

In our previous video, we reviewed three frontline therapies and the implications they can have in the second-line setting. In this discussion, we are going to focus on a specific patient who progressed on single-agent osimertinib and how we chose second-line therapy.

We had a 63-year-old female diagnosed with a stage IV EGFR exon 19–mutated lung adenocarcinoma with metastasis to the adrenal gland, liver, bone, and brain at presentation. This was in the times where osimertinib was the preferred single agent, back in December 2021. So she stayed on osimertinib, 80 mg daily, from December, 2021, until unfortunately, she developed more brain metastasis in February 2024. In hopes to keep her on osimertinib, we collaborated with our radiation oncology folks and she was able to receive Gamma Knife radiosurgery. She then stayed on osimertinib again from February until September 2024, when she developed leptomeningeal carcinomatosis.

We increased the osimertinib to 160 mg as studies at that time were showing benefit with the increased dosage in relation to intracranial metastasis and leptomeningeal disease. She did well for a bit on the increased dose of osimertinib. Unfortunately, she developed neurologic symptoms, and further imaging revealed she had more disease progression. We found new intracranial lesions as well as a cervical dural enhancement with neurologic symptoms that did appear, such as paralysis of her right eye and a left foot drop. And here's the CT imaging at the time of progression. You can see that even though she had the intracranial metastasis, she also developed an enlarging right lung lesion.

So lucky for her, this occurred around the same time that the MARIPOSA-2 trials were being discussed, and approval for carboplatin, pemetrexed, and amivantamab occurred in September 2024 for patients with EGFR-mutant non–small cell lung cancer, exon 19, exon 20, or EGFR 21-L858R. Amivantamab is a fully human immunoglobulin-based, or IgG-based bispecific antibody with immune cell directing activity that targets epidermal growth factor receptor mutations and is a mesenchymal-epithelial transition, or MET mutation, with amplifications in non–small cell lung cancer.

Data showed that amivantamab plus chemotherapy and amivantamab plus lazertinib and chemotherapy significantly improved progression-free survival versus chemotherapy and osimertinib alone, with a 52% and 56% lower risk of disease progression. The objective response rate was significantly higher for amivantamab plus chemotherapy, and amivantamab plus lazertinib plus chemotherapy, versus chemotherapy alone. And the data here was 64 and 63% with the combination arms, versus 36% with the single platinum doublet chemotherapy. The median intracranial progression-free survival was 12.5 months and 12.8 months, versus the 8.3 months for amivantamab plus chemo, and amivantamab plus lazertinib plus chemo, versus chemotherapy alone.

Options for this patient at the time of progression included whole brain and spine radiation versus systemic therapy. We chose to pursue systemic therapy, which was started in December of 2024. Approximately six weeks later, both CT scans, spine MRI and brain MRI showed a treatment response. The patient remains on treatment. She did receive platinum doublet plus amivantamab, and is now on pemetrexed and amivantamab maintenance and is doing really great. She still has a little bit of weakness but is ambulating with a walker and continues in physical therapy to this day.

So when we're thinking about these treatment options for our patients, we also have to be mindful of the toxicity and the complications that come with these regimens because they can be life-limiting for the patient. Forty-two percent of patients have infusion reaction with cycle 1, day 1. They develop rash, nail toxicity. We can have low blood counts. A lot of them develop bilateral lower extremity peripheral edema, cough, fatigue, stomatitis, constipation, and elevation of their liver enzymes. We have learned over time, we actually here at Washington University did amivantamab as part of another trial, so we were actually able to see this before it was FDA approved.

We became quite good at managing the toxicities; however, since the approval of carboplatin, pemetrexed, and amivantamab, the sponsors have also done the SKIPPirr and COCOON trials, and this is currently helping us be proactive about the management of these toxicities. So essentially for infusion reactions, we have started to develop plans where we give 8 mg of dexamethasone, twice a day, two days before chemo, the day before chemo with amivantamab. And then the day of treatment, they actually get 8 mg of dexamethasone orally and another 10 mg in the IV before infusion. We also think about using medications such as antihistamines, antipyretics, prior to infusion.

So Mary Ellen, I guess the question I would have for you, do you have any other thoughts or words of wisdom in regards to pretreatment in these infusion reactions?

Mary Ellen Flanagan:

Yeah, I think we were very fortunate here. I know, myself, and I know you two ladies do as well, we lean on our amazing thoracic pharmacy staff to really help us, and one thing that I add is the addition of antihistamine, like we've used montelukast successfully. In fact, I just had my first patient not react to her cycle 1, day 1 amivantamab, and I did have her take montelukast in conjunction with the dexamethasone for a few days leading up to treatment.

Hailey Hunter:

That's great. So she had no infusion reaction with cycle 1, day 1 –

Mary Ellen Flanagan:

Right. Right.

Hailey Hunter:

... which up until these managements was pretty unheard of.

Mary Ellen Flanagan:

Of course. Yeah.

Samantha Conlin:

Yeah, that's pretty impressive. I think I've still yet to have one that hasn't reacted. So props to you, Mary Ellen.

Hailey Hunter:

Another huge thing when it comes to the delivery of amivantamab is teaching the patients essentially how to manage a rash. The rash can happen with cycle 1, day 1. It can also occur later on in the cycles. The rashes may change. It may start on the legs and the trunk, and move to the scalp. So we have, again, pulled in data from SKIPPirr, COCOON. We also have a really good dermatology department here at Washington University that also trials EGFR toxicities and management. So we are utilizing doxycycline or minocycline, 100 mg, twice daily. We start this with cycle 1, day 1. We teach our patients to use chlorhexidine or bleach soaks on their fingernails and their toenails. Again, they would do this daily. We educate them on the use of ceramide lotions, daily, limiting sun exposure. Typically, about 3 to 4 months into the regimen, some people develop a pretty awful scalp lesion, and at that time we would institute a topical clindamycin shampoo or lotion that they put on their scalp prior to bedtime. And this is to avoid that area becoming infected and requiring antibiotics.

Sammy, do you have any other common side effects that you see with this MARIPOSA regimen?

Samantha Conlin:

So in my experience, as we already spoke about the transfusion reactions, especially with those first two cycles, are I'd say 100%, but the data suggests maybe half as much. But finding ways to manage those, we're getting better at that, and feeling more comfortable working with these medications. And then of course, the skin rash and a little bit later in the cycles, it's important again that we are able to educate our patients. I truly feel that knowledge is power and that educating these patients on how to take their antibiotics proactively, how to use the rinses and the chlorhexidine soaks regularly can prevent these more severe skin reactions from occurring before they escalate and need more intervention.

Hailey Hunter:

The other thing too, it's important sometimes we send the patients or give the patients a triamcinolone ointment just in the case the rash becomes itchy or bothersome to the patient. It's good for them to have a tube of that at home to use as needed, so their lifestyle is minimally changed.

Samantha Conlin:

And I think sometimes it's important to let these patients know, of course these paronychias that can happen. Sometimes I'll find patients going to their primary. It's like, you need to be calling us. We're the ones that are causing these problems and we may manage things differently than what a primary care office, for instance, may do. And so, again, I think just that education is so important in this setting.

Hailey Hunter:

Absolutely. So I included some pictures just so we can understand fully the toll these rashes can take on patients. This is a scalp rash that eventually became infected. The patient does the clindamycin shampoo and then oftentimes requires antibiotics. So beyond the minocycline and doxycycline regimen, we would have to give a Bactrim, double strength antibiotic to help these if they do become infected so that the patient doesn't wind up with a secondary infection that can also make them sick and ultimately lead to missing doses of both chemotherapy and amivantamab.

Samantha Conlin:

By the time we get to this point, I was going to say, then we're running into delaying care because we can't give chemo while we have these infections going on. So it's a trickle effect I think.

Hailey Hunter:

Absolutely.

Mary Ellen Flanagan:

Yeah, I was going to echo that, what you two ladies just said is – and I say this to patients, "I'm not saying this to scare you or give you an ultimatum, but this could happen." And we've had to hospitalize patients, and I do so to encourage compliance with the prophylactic care because it can spiral out of control quickly and cause treatment delays. And I think we can all agree none of our patients want to delay their treatment. So I think as both of you have mentioned, education is so important.

Hailey Hunter:

Absolutely. The picture here, this is a patient in real clinical time. This was cycle 24 of single-agent amivantamab. So he had already had too much toxicity from maintenance pemetrexed, so he's now just receiving amivantamab infusions. You can see here, the picture without the shoe, he developed a paronychia. He went on to receive silver nitrate therapy. After the nitrate therapy... And he did exactly what he was supposed to do, he was dressing it, he was using the ointments that were prescribed and unfortunately it just developed into an infection.

So on the left there with the shoe on or on the right, you could actually see, after he underwent excision of the pyogenic granuloma and completed yet another course of antibiotics. So that picture with the shoe is approximately 1 week after the excision of the granuloma, and you can see it's quite a bit better, but this resulted ultimately in approximately a 6-week delay in the treatment with amivantamab.

Samantha Conlin:

Wow.

Hailey Hunter:

Yeah, and it's important that we understand the dosing that occurs with amivantamab. There's great guidelines on how to complete dose reductions. It goes down by one dose reduction with each grade 3 or 4 toxicity, and so there's a lot of really great management information on the manufacturer website as well.

Mary Ellen Flanagan:

How do you manage that as far as knowing when to hold or when to dose reduce? Or is it patient specific?

Hailey Hunter:

Absolutely. If it's really limiting the performance status of the patient, you hold the drug and wait until the patient's feeling better ultimately, and then you make that decision with them. Do they want to restart this treatment? In the last case, the patient had been on it for 24 cycles, so we would definitely push him forward in pursuing further amivantamab because it's containing his cancer, right? But it's definitely a conversation that you need to have with your patient, as long as it's not too limiting or interfering with their daily life. For me, with a grade 3 or 4 toxicity, that's telling me to go ahead and hold the drug, let the patient recover either back to baseline or to grade 1, and then again, have that conversation with the patient. And also, are you going to follow through with your skincare? Are you going to follow through with your soaks? Helping them, empower them to be proactive as well.

So with a MARIPOSA-2 regimen, I think it's very important that the providers understand how to manage the infusion reactions. I would say with cycle 1, day 1 and day 2, essentially, that's probably your biggest factor with these treatment regimens, making sure that the treatment rooms are very aware the patient's coming, the toxicity and side effects occurring with amivantamab and infusion reactions. I also run a list of all side effects with the patient prior to them receiving cycle 1, day 1, in the treatment room. I teach them about treatment-related skin toxicities and, again, discuss the education associated with that, the steroid ointments, the daily use of antibiotics, and then to call, definitely, with any skin changes, nail changes. Call us, again, not the primary care provider, so that we can either seek dermatology approval, see the patient in clinic ourselves, and then figure out what we need to do with the dosing. And then modifying the dose and the dose escalations based off the patient's tolerability, what their toxicity looks like. These are all things that a provider needs to be very well versed in to treat with a MARIPOSA-2 regimen because it can be a very effective treatment option.

Samantha Conlin:

Thank you so much, Hailey. So this concludes our discussion of the case study, including the MARIPOSA-2. I'd like to thank Mary Ellen and Hailey for joining me today, and for more information and to view our other discussions on Updates on Second-Line EGFR-Mutated Non–Small Cell Lung Cancer, please visit JADPRO.com.