AMIVANTAMAB chemotherapy extended median overall survival (OS) by more than 6 months compared with chemotherapy alone in patients with advanced epidermal growth factor receptor (EGFR) exon 20 insertion (Ex20ins) non-small cell lung cancer (NSCLC) in the final OS analysis of the Phase III PAPILLON trial.
The international Phase III PAPILLON study randomised 308 participants with previously untreated, advanced EGFR Ex20ins NSCLC to first-line amivantamab plus carboplatin and pemetrexed or chemotherapy alone. Participants were assigned to the amivantamab chemotherapy group (n=153) or chemotherapy group (n=155).
On protocol crossover was permitted, allowing participants receiving chemotherapy to receive amivantamab monotherapy after confirmed disease progression. OS was a key secondary endpoint, with the protocol specified final analysis conducted after approximately 210 deaths.
At the 20 March 2026 clinical cut-off, 12% of participants remained on treatment in the amivantamab chemotherapy group, compared with none in the chemotherapy group.
After a median follow-up of 48.6 months, median OS was 34.3 months with amivantamab chemotherapy compared with 27.9 months with chemotherapy alone. This represented a numerical extension of more than 6 months and a 13% reduction in the risk of death, although the difference was not statistically significant (hazard ratio (HR): 0.87; 95% CI: 0.66–1.14; p=0.307).
The chemotherapy group had substantial subsequent exposure to amivantamab, with 97 of 128 participants who discontinued treatment because of progressive disease receiving second-line amivantamab monotherapy. Of these, 87 received treatment according to protocol.
A prespecified analysis accounting for on protocol crossover produced a larger estimated treatment effect. Adjusted median OS for the chemotherapy group was 22.1 months, while the adjusted OS comparison favoured amivantamab chemotherapy (HR: 0.57; 95% CI: 0.39–0.82; nominal p=0.003).
The safety profile of intravenous amivantamab chemotherapy remained consistent with previous reports, while patient reported outcomes favoured the combination, including a longer time to worsening across several key symptom measures.
The investigators reported that the PAPILLON results represented the longest median OS reported to date in advanced EGFR Ex20ins NSCLC. Despite extensive use of subsequent amivantamab in the chemotherapy group, first-line amivantamab chemotherapy produced a clinically meaningful extension in median OS.
The findings further supported amivantamab chemotherapy as a foundational first-line regimen for patients with advanced EGFR Ex20ins NSCLC.
Reference
Kim C et al. First-line Amivantamab-chemotherapy vs Chemotherapy in NSCLC with EGFR Exon 20 Insertions: Overall Survival from PAPILLON. Abstract PL03.03. WCLC Congress; 12-15 September 2026.
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