Dr Girard on the Efficacy of First-Line Amivantamab Plus Chemotherapy in EGFR Exon 20 Insertion+ NSCLC

Nicolas Girard, MD, PhD, professor of Respiratory Medicine, Versailles Saint Quentin University, professor, head, the Curie-Montsouris Thorax Institute, Institut Curie, discusses primary efficacy results from the phase 3 PAPILLON trial (NCT04538664) of amivantamab (Rybrevant) plus chemotherapy in EGFR exon 20 insertion–mutated advanced non–small cell lung cancer (NSCLC).

In addition to having known immune cell–directing activity in NSCLC, the EGFR x MET bispecific antibody amivantamab previously demonstrated clinical activity and tolerability when administered alongside carboplatin or pemetrexed in patients with this disease type who progressed on platinum-based chemotherapy, according to results from the phase 1 CHRYSALIS study (NCT02609776). Based on these data, the randomized, global PAPILLION study evaluated the efficacy of amivantamab plus chemotherapy compared with chemotherapy alone. Notably, patients in the chemotherapy arm were allowed to cross over to second-line amivantamab monotherapy upon disease progression.

Initial results from the study demonstrated that amivantamab plus chemotherapy met the study's primary end point of progression-free survival (PFS) vs chemotherapy alone in this population. Patients treated with the combination experienced a median PFS of 11.4 months compared with 6.7 months for those who received chemotherapy, translating to a 60.5% reduction in the risk of progression or death (HR, 0.395; 95% CI, 0.30-0.53; P< .0001).

Long-term efficacy was also demonstrated by the combination, which was in line with previous data. Despite the fact that 65 patients crossed over to amivantamab monotherapy, the combination elicited higher response rates, prolonged duration of response, and longer time to second progression.

Although overall survival data were not mature at the time of this analysis, a trend toward improved OS was observed with the combination vs chemotherapy alone. The median OS was not reached in combination arm, vs 24.4 months in the chemotherapy alone arm. More follow-up is needed to confirm the regimen's OS benefit.

Overall, these results support the use of amivantamab plus chemotherapy as a new standard of care in the first-line setting for patients with EGFR exon 20 insertion–mutated NSCLC.