Amivantamab and Chemotherapy Prolong OS in Previously Untreated EGFR ex20ins NSCLC
Posted: Friday, September 25, 2026
Amivantamab in combination with chemotherapy extended overall survival compared with chemotherapy alone in patients with advanced non–small cell lung cancer (NSCLC) and EGFR exon 20 insertion mutations who were being treated in the first-line settings. Findings from the phase III PAPILLON trial were presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC; Abstract PL03.03).
The study authors, led by Chul Kim, MD, MPH, the Director of Thoracic Oncology at MedStar Georgetown University Hospital and an Associate Professor at Georgetown University, noted that the study demonstrated the longest reported median overall survival to date in patients with EGFR exon 20 insertion–mutant advanced NSCLC.
Patients enrolled in the study had previously untreated advanced NSCLC with EGFR exon 20 insertion mutations. They were randomly assigned 1:1 to receive either intravenous amivantamab and chemotherapy (n = 153) or chemotherapy alone (n = 155). Crossover from the control arm to receive second-line amivantamab monotherapy was allowed after disease progression was confirmed.
As of the data cutoff, 12% of patients in the investigational arm were still on treatment vs 0% in the control arm. Seventy-six percent of patients in the chemotherapy arm received second-line amivantamab monotherapy (87 on protocol, 10 off-protocol).
At a median follow-up of 48.6 months, the median overall survival was 34.3 months (95% confidence interval [CI] = 27.0–40.8) with amivantamab and chemotherapy compared with 27.9 months (95% CI = 24.0–32.4) with chemotherapy alone (hazard ratio [HR] = 0.87; 95% CI = 0.66–1.14; P = .307). After adjusting for on-protocol crossover, the median overall survival in the control arm was 22.1 months (95% CI = 16.4–27.6), resulting in an HR of 0.57 (95% CI = 0.39–0.82; nominal P = .003). Overall survival findings also generally favored the amivantamab arm across predefined subgroups.
The combination arm had a safety profile that was consistent with prior reports for amivantamab, before prophylactic measures were optimized. Patient-reported outcomes also favored the combination arm, and several key symptom scales showed a prolonged time to worsening symptoms with the addition of amivantamab.
