Dr Spira Details Future Directions for Amivantamab in NSCLC

“We also know that patients who are on [amivantamab] may need a break, and there have been some good abstract presentations so far showing that even if patients get a break from therapy, they actually benefit as well.”

Alexander I. Spira MD, PhD, FACP, FASCO, codirector, Virginia Cancer Specialists Research Institute; director, Thoracic and Phase I Program; clinical assistant professor, Johns Hopkins School of Medicine, details future directions for amivantamab-vmjw (Rybrevant) following data from the phase 3 MARIPOSA study (NCT04487080) evaluating the agent in patients with untreated EGFR-mutated locally advanced or metastatic non–small cell lung cancer (NSCLC).

The study compared amivantamab plus lazertinib (Lazcluze) vs osimertinib (Tagrisso) alone in patients with previously untreated EGFR-mutated locally advanced or metastatic NSCLC. At a median follow-up of 31.1 months, the median overall survival (OS) was not estimable (NE; 95% CI, NE-NE) among patients from the amivantamab/lazertinib arm (n = 429) vs 37.3 months (95% CI, 32.5-NE) in those treated with osimertinib (HR; 0.77; 95% CI, 0.61-0.96; P =.019). Of note, the 24- and 36-month OS rates were 75% (95% CI, 71%-79%) and 61% (95% CI, 56%-67%) in the combination arm, respectively, compared with 70% (95% CI, 65%-74%) and 53% (95% CI, 47%-59%) in the osimertinib arm. Findings from the study supported the August 2024 FDA approval of the combination for the first-line treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.

Spira explains that future directions for amivantamab depend on data from the phase PALOMA-3 study (NCT05388669), which is investigating subcutaneous amivantamab/lazertinib vs the intravenous combination. He notes that data from the PALOMA-3 study may help lead to less time for patients in the clinic, a reduction in infusion-related reactions, and mitigation of other toxicities. In the phase 2 COCOON study (NCT06120140), investigators are evaluating the effect of enhanced vs standard dermatologic management of selected dermatologic adverse effects in patients with EGFR-mutated locally advanced or metastatic NSCLC treated with first-line amivantamab/lazertinib.

Spira also explains that patients treated with amivantamab may require breaks. He concludes that when patients take a temporary break after receiving therapy for a few months, there is not necessarily a detriment to taking the break.