2MO Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR exon 20 insertion-mutated advanced NSCLC: Analysis of post-progression endpoints from PAPILLON

Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. In PAPILLON (NCT04538664), ami plus carboplatin-pemetrexed (ami-chemo) significantly prolonged progression-free survival (PFS) vs chemo in patients (pts) with EGFR Ex20ins advanced NSCLC (Zhou NEJM 2023). We evaluated post-progression secondary endpoints of time to treatment discontinuation (TTD) and time to subsequent (systemic anticancer) therapy (TTST). 308 pts were randomized (ami-chemo: 153; chemo: 155). Chemo-randomized pts were allowed crossover upon blinded independent central review (BICR)-confirmed progression. TTD and TTST were evaluated based upon site reporting of participant treatment changes. At a median follow-up of 14.9 months (mo), 54% (83/153) and 85% (131/155) of pts discontinued treatment in the ami-chemo and chemo arms, respectively. Median TTD was 13.2 mo for ami-chemo vs 7.5 mo for chemo (HR, 0.38 95% CI, 0.28–0.51; P<0.0001). Median TTST was 17.7 mo for ami-chemo vs 9.9 mo for chemo (HR, 0.35 95% CI, 0.25–0.49; P<0.0001). These findings are consistent with PFS after first subsequent therapy (PFS2; HR, 0.49 95% CI, 0.32–0.76; P=0.001) and interim overall survival (HR, 0.67 95% CI, 0.42–1.09; P=0.11) favoring ami-chemo vs chemo (Girard Ann Oncol 2023). Among pts who discontinued, 52% (43/83) and 72% (94/131) in the ami-chemo and chemo arms started a subsequent therapy, most common being chemotherapy (ami-chemo; 30% 13/43) and ami monotherapy (chemo; 76% 71/94). 17% (11/63 with disease progression) of pts continued treatment beyond progression in the ami-chemo arm, median duration after progression of 40.4 weeks (95% CI, 8.7–NE). Among 71 chemo-randomized pts who received second-line ami monotherapy, 65 pts were part of the study crossover arm, with 6 receiving ami off protocol. Among the 65 pts in the crossover arm, 46% (30/65) discontinued ami monotherapy. Median treatment duration was 4.9 mo (range, 0–18.2), with a median TTD of 9.7 mo (95% CI, 6.7–11.0). Ami-chemo significantly prolonged TTD and TTST vs chemo. Ami-chemo is the new first-line standard of care for EGFR Ex20ins-mutant advanced NSCLC.