PAPILLON Phase 3 Trial Reports 34.3-Month Median OS With Amivantamab-Chemotherapy in EGFR Ex20ins NSCLC

The PAPILLON trial randomized 308 patients 1:1 to amivantamab-chemotherapy or chemotherapy alone, with overall survival as a key secondary endpoint. At 48.6 months median follow-up, the unadjusted hazard ratio was 0.87 (95% CI 0.66-1.14). After 76% of progressed chemotherapy patients crossed over to second-line amivantamab, inverse probability of censoring weighting adjustment yielded an HR of 0.57 (nominal P=0.003). Patient-reported outcomes also favored the combination for time to symptom worsening.

EGFR exon 20 insertions comprise roughly 12% of EGFR-mutated NSCLC and historically carried poor prognosis with limited targeted options. The 6.4-month numerical gain aligns with prior progression-free survival benefit reported in the same trial. However, the modest unadjusted survival difference reflects the high crossover rate, a pattern seen in other first-line lung cancer studies where subsequent therapy dilutes intention-to-treat estimates.

Longer-term data and full peer-reviewed publication are required to confirm durability and generalizability. Ongoing development of subcutaneous amivantamab with prophylactic strategies may improve tolerability. Future trials should evaluate sequencing with emerging agents and assess real-world outcomes in populations underrepresented in PAPILLON.