Amivantamab Presents an Exciting Treatment Opportunity in NSCLC

In less than a month, from August 20 to September 19, amivantamab (Ami; Rybrevant, Johnson & Johnson) received 2 approvals from the FDA for use in non–small cell lung cancer (NSCLC). Here we continue our discussion with Joshua K. Sabari, MD, oncologist with NYU Langone Perlmutter Cancer Center, about the August approval, which saw amivantamab plus lazertinib (Lazcluze, Janssen Biotech) receive an indication as part of a chemotherapy-free first-line regimen in patients with exon 19 deletions or exon 21 L858R substitution mutations. Data from the MARIPOSA study (NCT04487080) were used for this approval.

Sabari has extensive experience with amivantamab development and was in investigator with the PAPILLON study, data of which were used as the basis of the March 1 approval of amivantamab plus chemotherapy for first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

This transcript has been lightly edited.

Transcript

What treatment gaps are filled by the approval of a first-line chemotherapy-free regimen for this type of NSCLC?

I think now we have 3 FDA-approved regimens in the frontline setting, and we have to have discussions with our patients with common EGFR mutations. We just heard about the recent approval of MARIPOSA. We have the approval of FLAURA, obviously, with osimertinib as a single agent, as well as osimertinib plus chemo [in] FLAURA2. So the question then becomes, who to utilize what regimen in, and I think we need further data to better understand this. We saw some data presented at ASCO looking at high-risk patient populations, patients with brain metastases; comutations, for example; and p53 patients who are CtDNA [circulating tumor DNA]–positive or who don't clear their CtDNA, for example. These are all high-risk groups, in my opinion. And when we look at the MARIPOSA data in a subset analysis, the addition of amivantamab to lazertinib seems to benefit all of these high-risk subsets, these high-risk patient groups.

I think you need to have a discussion with your patient, and at the end of the day, if the patient is willing to utilize the most aggressive therapy—including both outcome data, progression-free survival, as well as trend towards overall survival, but as well as increased toxicity—I think Ami plus lazertinib is probably the most aggressive regimen available in the frontline setting that is now FDA approved. So really it comes down to a discussion with your patient in the office to try to understand their goals and to align their goals with their therapeutic options.

It's interesting that first-line chemotherapy is really not a standard of care, in my opinion, in the EGFR-mutant population. If you think about patients with EGFR mutation, we've really wanted to utilize targeted therapies. And even going back 10,12 years, when you compare first-, second-generation EGFR inhibitors—really first-gen inhibitors to chemotherapy—you see a significant improvement in PFS, as well as overall survival. And then with the approval of third-generation EGFR inhibitors, these were studied against first-gen, such as gefitinib and erlotinib.

The problem is, our therapies have become so successful. Osimertinib as a third generation EGFR TKI is such a good therapy—median progression-free survival about 22 months in the exon 19 [deletion] population, about 14.4 months in the L858R population, and 18.9 months overall in all-comers in the FLAURA study—in order to build upon that, the FLAURA2 trial was done with the addition of chemotherapy. But to be honest, adding chemotherapy I think moves away from a targeted therapy paradigm. I think chemotherapy has known toxicities. We're all comfortable managing them. But more importantly, chemotherapy is an option in the second-line setting and has been classically used for many years in patients who have progressed on osimertinib.

I think in the MARIPOSA regimen utilizing 2 EGFR-directed strategies with different mechanisms of action is a more academic, as well as more exciting, opportunity for patients. Again, there are different and unique side effects with amivantamab compared to chemotherapy. So it's a chemotherapy-free regimen. It's different, but it also does have some side effects that we'll talk about.