Amivantamab plus Chemotherapy: New Standard for EGFR Exon 20–Mutated NSCLC

Amivantamab monotherapy has been approved for the treatment of patients with advanced non–small-cell lung cancer (NSCLC) with EGFR exon 20 insertions who have had disease progression after platinum-based chemotherapy. In the industry-supported, international, randomized, phase 3 PAPILLON trial, researchers compared first-line therapy with amivantamab plus platinum-based chemotherapy versus chemotherapy alone in 308 patients with EGFR exon 20 insertion–mutated advanced NSCLC.

Amivantamab was given weekly for 4 weeks then every 3 weeks until disease progression. Chemotherapy consisted of carboplatin and pemetrexed given for 4 cycles followed by maintenance pemetrexed given every 3 weeks until disease progression.

At a median follow-up of 14.9 months, median progression-free survival (PFS) — the primary outcome — was 11.4 months with amivantamab–chemotherapy versus 6.7 months with chemotherapy alone (hazard ratio, 0.40; 95% CI 0.30–0.53; P< 0.001). PFS rates were higher with combination therapy at 6 months (77% vs. 51%), 12 months (48% vs. 13%), and 18 months (31% vs. 3%,). The objective response rate was also significantly improved with amivantamab–chemotherapy compared with chemotherapy alone (73% vs. 47%; rate ratio 1.5; P<0.001). Overall survival was not yet mature at the time of the interim analysis.

The predominant adverse events associated with amivantamab–chemotherapy were reversible hematologic and EGFR-related toxic events that required frequent dose interruptions and led to discontinuation of therapy in 7% of patients.