Overall survival from PAPILLON

At WCLC 2026, Prof Chul Kim presented the final overall survival analysis of the phase III PAPILLON trial, evaluating first-line amivantamab plus chemotherapy versus chemotherapy alone in patients with treatment-naïve, locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.

PAPILLON previously met its primary endpoint, demonstrating improved progression-free survival (PFS) with amivantamab plus chemotherapy. The final analysis now provides longer-term survival data after a median follow-up of 48.6 months. Median overall survival was 34.3 months with amivantamab plus chemotherapy versus 27.9 months with chemotherapy alone. At three years, 47% of the patients receiving the combination were alive, compared with 38% in the chemotherapy arm. The OS hazard ratio was 0.87, statistical significance was not reached.

Interpretation of overall survival is complicated by the high degree of crossover permitted by the trial protocol. Among patients in the chemotherapy arm who discontinued treatment because of disease progression, 76% crossed over to second-line amivantamab. A crossover-adjusted analysis estimated a median overall survival of 22.1 months for chemotherapy alone and showed an overall survival benefit with first-line amivantamab plus chemotherapy (HR 0.57).

The benefit extended beyond first disease progression, with progression free survival prolonged by more than ten months with the combination. The safety profile was consistent with previous reports, with no new safety signals identified. The trial was conducted before the evaluation of subcutaneous amivantamab and the introduction of more recent prophylactic supportive strategies. Patient-reported outcomes also favoured amivantamab plus chemotherapy, with a longer time to worsening of symptoms including pain and dyspnoea, as well as a longer time to symptomatic progression.

Overall, these long-term results support amivantamab plus chemotherapy as a first-line treatment option for EGFR exon 20 insertion-mutated NSCLC. The treatment landscape is continuing to evolve, with zipalertinib plus chemotherapy and emerging first-line data of sunvozertinib providing additional treatment perspectives. As more options become available, further data on long-term survival and tolerability, CNS activity and outcomes according to the location of the EGFR exon 20 insertion will be important to inform treatment selection.