Amivantamab-Chemotherapy in Non-Small Cell Lung Cancer with EGFR Exon 20 Insertions: Impact of Treatment Crossover and Other Endpoints from the Phase III PAPILLON Study.
Publication Title
Target Oncol
Document Type
Article
Publication Date
11-1-2025
Keywords
oregon; chiles
Abstract
BACKGROUND: In the PAPILLON study, first-line amivantamab-chemotherapy in epidermal growth factor receptor (EGFR) exon 20 insertion-mutated non-small cell lung cancer demonstrated significantly prolonged progression-free survival and favorable overall survival over chemotherapy; a consistent benefit was also observed across some secondary endpoints. However, the complete clinical benefit of first-line amivantamab-chemotherapy is not fully understood, nor is the survival advantage in the presence of per-protocol crossover from chemotherapy to amivantamab after progression.
OBJECTIVE: We aimed to assess time to treatment discontinuation (TTD) and time to subsequent therapy (TTST), at the time of primary analysis for progression-free survival, and the effect of the crossover design on overall survival at the time of interim analysis.
METHODS: In the phase III PAPILLON study, 308 participants were randomized (amivantamab-chemotherapy, n = 153; chemotherapy, n = 155). Intravenous amivantamab was administered every 3 weeks. Chemotherapy was administered as carboplatin for four cycles and pemetrexed until disease progression. TTD and TTST were evaluated using Kaplan-Meier and Cox proportional hazards models. Crossover-adjusted survival estimates were generated using three established statistical methods.
RESULTS: At a median follow-up of 14.9 months, median TTD was 13.2 versus 7.5 months for amivantamab-chemotherapy versus chemotherapy (hazard ratio [HR] 0.38 [95% confidence interval 0.28-0.51]; nominal p < 0.0001). Median TTST was 17.7 versus 9.9 months (HR 0.35 [95% confidence interval 0.25-0.49]; nominal p < 0.0001). A total of 65/155 participants crossed over from chemotherapy to amivantamab after progression. The crossover-adjusted overall survival continued to demonstrate a favorable survival benefit for amivantamab-chemotherapy versus chemotherapy with HRs of 0.52-0.60, which is more pronounced than the planned interim intention-to-treat overall survival (HR of 0.67; 95% confidence interval 0.42-1.09).
CONCLUSIONS: In PAPILLON, TTD and TTST were substantially longer for amivantamab-chemotherapy versus chemotherapy at primary analysis (cut-off on 3 May 2023). Crossover-adjusted analyses of the planned interim overall survival demonstrated a greater benefit for amivantamab-chemotherapy versus chemotherapy, further supporting amivantamab-chemotherapy as the first-line standard of care in EGFR exon 20 insertion-mutated non-small cell lung cancer.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04538664.
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Pharmacy
Specialty/Research Institute
Pulmonary Medicine
DOI
10.1007/s11523-025-01182-0
