Amivantamab plus chemotherapy vs. chemotherapy as first-line treatment in Chinese mainland patients with EGFR exon 20 insertion non-small cell lung cancer: Subgroup analysis of the randomized PAPILLON trial

BACKGROUND: First-line amivantamab plus carboplatin-pemetrexed demonstrated efficacy and an acceptable safety profile in the PAPILLON trial (NCT04538664) in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 20 insertions; we report the efficacy and safety results of the Chinese mainland subgroup population from the PAPILLON study. METHODS: PAPILLON was a randomized, open-label, multicenter, phase 3 study comparing amivantamab plus carboplatin-pemetrexed therapy with standard of care carboplatin-pemetrexed, in patients with treatment-naïve, locally advanced, or metastatic non-small-cell lung cancer characterized by EGFR exon 20 insertion mutations. Between March 2021 and October 2022, 87 treatment-naïve patients were randomized in China (amivantamab plus carboplatin-pemetrexed, 39; carboplatin-pemetrexed, 48). The primary endpoint was progression-free survival as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors v1.1. Comparison between treatment groups was conducted using a stratified log-rank test, with hazard ratios estimated from a stratified Cox proportional hazards model. RESULTS: Progression-free survival was longer in the amivantamab plus carboplatin-pemetrexed group than in the carboplatin-pemetrexed group (median, 12.3 months, 95% confidence interval CI, 7.0 months to not evaluable vs. 6.7 months, 95% CI, 4.2-8.6 months; hazard ratio, 0.47; 95% CI, 0.26-0.85; nominal P = 0.0109). The 18-month progression-free survival rate was 33% with amivantamab plus carboplatin-pemetrexed and 12% with carboplatin-pemetrexed. The objective response rate was 71.8% (95% CI, 55.1-85.0%) with amivantamab plus carboplatin-pemetrexed and 48.9% (34.1-63.9%) with carboplatin-pemetrexed (odds ratio, 2.46; 95% CI, 1.01-5.98; nominal P = 0.0478). Median progression-free survival after first subsequent therapy was not evaluable for amivantamab plus carboplatin-pemetrexed and 18.8 months for carboplatin-pemetrexed (hazard ratio, 0.32; 95% CI, 0.11-0.88; nominal P = 0.0212). Interim overall survival analysis suggests about 42% improved chance of survival with amivantamab plus carboplatin-pemetrexed vs. carboplatin-pemetrexed. The most common adverse events with amivantamab plus carboplatin-pemetrexed were neutropenia, anemia, leukopenia, and rash. No new safety signals were observed. No patients discontinued amivantamab due to related adverse events. CONCLUSION: Results from the PAPILLON Chinese mainland population were consistent with the overall population and support the use of amivantamab plus carboplatin-pemetrexed in first-line treatment of Chinese patients with EGFR exon 20 insertion-mutated non-small cell lung cancer. TRIAL REGISTRATION: https://clinicaltrials.gov/; registration number, NCT04538664.