Impact of Amivantamab Dose Interruptions on Efficacy, Safety Among Patients With EGFR-Mutated Advanced Non-Small Cell Lung Cancer

Joshua Sabari, MD, NYU Langone Health, New York, New York, discussed exploratory analysis results from the phase 3 MARIPOSA study, as presented at the European Lung Cancer Congress 2024. 

Results demonstrated that early amivantamab dose interruptions did not adversely affect efficacy and safety outcomes of amivantamab plus lazertinib among patients with advanced, EGFR-mutated non-small cell lung cancer and this combination should be considered the new standard of care. 

Transcript:

Hi, I'm Josh Sabari, Thoracic Medical Oncology at NYU Langone Health, Perlmutter Cancer Center in New York, and I'm excited to talk to you about the effect of amivantamab dose interruptions on efficacy and safety of first-line amivantamab plus lazertinib in EGFR-mutated advanced non-small cell lung cancer. This is an update from the exploratory analysis from the MARIPOSA study, initially presented at ESMO. We saw this abstract presented at the [European Lung Cancer Congress] ELCC 2024.

As you recall, the MARIPOSA trial is a randomized, controlled trial of amivantamab, an EGFR and c-Met bispecific, plus lazertinib, a third-generation brain-penetrant EGFR [tyrosine kinase inhibitor] TKI, in combination with amivantamab. We looked at that compared to a control arm of osimertinib, osimertinib being a third-generation EGFR TKI, versus lazertinib as a single agent for contribution of components. We saw the data for MARIPOSA presented at ESMO with a hazard ratio of 0.7, so if you received amivantamab and lazertinib, median [progression-free survival] PFS of 23.7 months versus osimertinib alone of 16.6 months. 

Here in this abstract, we looked at some of the key adverse events, we also looked at the dose reduction rate and how that interfered or interacted with the outcome so, we really evaluated the association of amivantamab dose interruptions in the first 4 months to allow for steady state of this therapy with efficacy and safety outcomes for those receiving amivantamab and lazertinib. Among the 421 patients who received ≥1 dose of amivantamab, 49% had a dose interruption within the first 4 months. What was important to note was that outcomes were similar among patients with and without dose interruptions. If you were in the cohort who had a dose interruption in the first 4 months, the median progression-free survival was 23.9 months. If you were in the group who did not have any dose interruptions, the median progression-free survival was 23.7 months. And if you remember, all randomized patients [had a progression-free survival] of 23.7 months. 

To minimize bias, we really focused on evaluating outcomes after the first 4 months which we termed the "exposure period". When you look at some of the prevalence and severity of some of the key adverse events over time, clearly there is more toxicity in the first 4 months of therapy: things like [infusion-related reactions] IRR but also the rash, mostly grade 1 and 2, hovering about that 50% range. If you look at those who had interruptions versus those who did not have interruptions, similar rates of toxicity. Clearly those who had grade 3 toxicity had higher rates of dose interruptions, paronychia for example also hovering in that 50% range. Some of the other toxicities that we saw were hypoalbuminemia, which is a MET-mediated toxicity which may lead to peripheral edema or lower extremities swelling, that was in the first 4 months. When you look at months 5 to 8, the rate of adverse events drops significantly. The rate of rash for example goes down into that 30% range, paronychia in that 40% range, things like hypoalbuminemia in that 30% range as well.

How do these dose interruptions affect progression-free survival; at the end of the day are patients able to receive therapy and are we able to mitigate toxicity, and does it improve or affect the sort of outcomes for this patient population? The median progression-free survival after 4 months was similar between patients with and without dose interruptions. Here the multivariate analysis PFS hazard ratio was 1.06, so really no difference in the progression-free survival in those with dose interruptions versus those without. Median progression-free survival for those with dose interruptions was 27.5 months, median progression-free survival for those without dose interruptions was 25.7 months–so really no difference and I think it was really helpful to see that. 

Approximately half of patients treated with amivantamab and lazertinib did require a dose interruption in the first 4 months. We know that dose discontinuation rates were quite low and the prevalence of key adverse events, particularly things such as IRR, dermatitis, paronychia, and hypoalbuminemia, were highest in the first 4 months, mostly grade 1 and grade 2, and then declined over the next 4 months for both groups with dose interruptions and those without. There were no grade 4 or 5 adverse events. 

We know that median progression-free survival in this population is similar between patients with and without dose interruptions after 4 months. Amivantamab dose interruptions may be a meaningful way to manage some of the adverse events without compromising the efficacy of this regimen. Amivantamab and lazertinib represents a potential new standard of care for patients in the front-line setting for patients with EGFR-Exon 19 del and L858r mutant non-small cell lung cancer and this application is currently under review with the FDA. 

Source: 

Garcia Campelo MR, Cho BC, Girard N, et al. Effect of amivantamab dose interruptions on efficacy and safety of first-line amivantamab plus lazertinib in EGFR-mutant advanced NSCLC: Exploratory analyses from the MARIPOSA study. Presented at the European Lung Cancer Congress 2024; March 20-23, 2024. Prague, Czech Republic. Abstract 5MO