Amivantamab-chemotherapy demonstrates longest overall survival reported for lung cancer with EGFR mutation

by International Association for the Study of Lung Cancer

edited by Gaby Clark, reviewed by Robert Egan

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Results from the phase 3 PAPILLON study show that first-line amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) was associated with numerically longer overall survival compared with chemotherapy in patients with previously untreated advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (Ex20ins) mutations. The findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).

EGFR exon 20 insertions account for approximately 12% of EGFR-mutated NSCLC. In PAPILLON (NCT04538664), 308 participants with previously untreated Ex20ins advanced NSCLC were randomized 1:1 to amivantamab-chemotherapy (n = 153) or chemotherapy (n = 155). Participants in the chemotherapy arm were permitted to cross over to second-line amivantamab monotherapy after confirmed disease progression. Overall survival was a key secondary endpoint.

At the March 20, 2026, data cutoff, with a median follow-up of 48.6 months, median overall survival was 34.3 months with amivantamab-chemotherapy versus 27.9 months with chemotherapy (HR 0.87; 95% CI, 0.66–1.14; P = 0.307). This represents a numerical improvement of 6.4 months in median overall survival. Overall survival results generally favored amivantamab-chemotherapy across predefined subgroups.

Among 128 participants in the chemotherapy arm who discontinued because of progressive disease, 97 (76%) received second-line amivantamab monotherapy. After adjusting for on-protocol crossover using the prespecified inverse probability of censoring weighting (IPCW) model, amivantamab-chemotherapy demonstrated a significant survival benefit (IPCW HR 0.57; 95% CI, 0.39–0.82; nominal P = 0.003).

The safety profile of intravenous amivantamab-chemotherapy was consistent with prior reports of intravenous amivantamab before subcutaneous amivantamab and prophylactic adverse-event strategies were implemented. Patient-reported outcomes also favored amivantamab-chemotherapy, with prolonged time to worsening across several key symptom scales.

"PAPILLON demonstrated the longest reported median overall survival to date in EGFR exon 20 insertion-positive advanced NSCLC with first-line amivantamab-chemotherapy," said Chul Kim, MD, of the Division of Hematology and Oncology at Georgetown Cancer Institute in Washington, D.C.

"While crossover likely attenuated the hazard ratio-based overall survival estimate, the adjusted analysis showed a substantially longer estimated survival benefit, supporting amivantamab-chemotherapy as a foundational first-line regimen for patients with Ex20ins advanced NSCLC."

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OncologyPulmonary medicine Provided by International Association for the Study of Lung Cancer Who's behind this story?

Gaby Clark

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Citation: Amivantamab-chemotherapy demonstrates longest overall survival reported for lung cancer with EGFR mutation (2026, September 13) retrieved 14 September 2026 from https://medicalxpress.com/news/2026-09-amivantamab-chemotherapy-longest-survival-lung.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.