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Amivantamab/Lazertinib Still Effective in EGFRm NSCLC Despite Dose Interruptions

*March 2024*

The phase 3 MARIPOSA trial (NCT04487080) evaluating a regimen of amivantamab-vmjw (Rybrevant) and lazertinib vs standard-of-care osimertinib (Tagrisso) for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC) had promising results, showing the superiority of amivantamab/lazertinib over osimertinib.

The combination demonstrated a longer progression-free survival (PFS) and duration of response (DOR) with a positive overall survival trend. However, questions about the regimen remain.

One further area of investigation foucuses on the efficacy of the combination regimen if the dose needs to be interrupted. This was explored in a subset analysis presented at the 2024 European Lung Cancer Congress.

According to Alex Spira, MD, PhD, FACP, the analysis identified that patients who received dose interruptions within the first 4 months of treatment had a median PFS similar to patients who did not receive dose interruptions. The median PFS in the dose interruption group was 23.9 months (95% CI, 18.5-not evaluable [NE]) compared with 23.7 months (95% CI, 18.4-NE) in patients who did not have dose interruptions. The overall response rate in the dose interruption group was 87% (range, 81%-91%) compared with 89% (range, 84%-93%) in the group without dose interruptions. Moreover, the median DORs were 25.8 months (range, 16.7-NE) and 26.1 months (range, 20.1-NE) in the groups with or without dose interruptions, respectively.1

In an interview with Targeted OncologyTM, Spira, thoracic oncologist at Virginia Cancer Specialists, discussed this subset analysis and what it means for the treatment landscape of EGFR-mutant NSCLC.

Targeted Oncology: What is the current treatment landscape of EGFR-mutant NSCLC?

Spira: In the frontline setting, the current treatment landscape for [patients who are] newly diagnosed is osimertinib. We recently had the FDA approval of FLAURA-2, which is chemotherapy in conjunction with osimertinib. Right behind it, not yet approved, but we are awaiting that soon, we hope and believe, is the combination of amivantamab plus lazertinib also in frontline setting.

What was the goal of the analysis? Can you summarize the findings?

The initial MARIPOSA study, as published and presented, demonstrated amivantamab/lazertinibwas more effective than osimertinib in the newly diagnosed lung cancer population. Not a lot of surprises here, and we have seen it both in MARIPOSA as well as in MARIPOSA-2 [NCT04988295] in the second-line setting. With the addition of amivantamab, which is a bispecific EGFR MET[-directed] antibody, we expected and did have more [adverse] effects.

The typical [adverse] effects are rash, cutaneous reactions, and immune-related adverse events. The most concerning thing over time are not the immune-related reactions, because that typically [occurs] just [with] the first dose. [The most concerning thing is] how we manage people that need dose interruptions. This study began to look a little bit more in detail at the subset of those patients that required dose interruptions during treatment with amivantamab and lazertinib.

How do these findings impact the original findings from MARIPOSA?

What is found in MARIPOSA that dose interruptions do not affect outcomes that much. If we look at a couple of things, patients who got those interruptions who didn’t get those interruptions, we did not see much of a difference in response rates and duration of response; they were pretty much identical. The [adverse] effects were as expected, and the progression-free survival [curves are] basically identical. At 24 months, it was 52% in both arms, with no differences whatsoever.

The good news is, if you decide to interrupt [patients] for whatever reason, patients did just as well. The concern is if they have to stop the drug, [they will] lose some of the benefits. But clearly, we are still getting enough dose intensity and patients can still do well, even with occasional dose interruptions. On the study, what we found was physicians could do dose interruptions as they needed. If a patient’s having too many [adverse] effects, if they traveled, if a patient required a dose interruption… we should feel very comfortable that it’s okay to hold the dose as needed for adverse events, and patients should do just as well.

Are there next steps moving forward from this research?

This research here was just to establish a subset analysis. MARIPOSA was a positive study. Of course, now there are going be a lot of different subset analyses [that] look at different things. We will be looking at patients who might benefit more or less by intensification, therapy, some of the [adverse] effects as well, how do you manage that? We are seeing a lot of these things. I expect a lot of subgroup analyses over the months and years to come.