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.
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Sanborn Rachel E, Zhou Caicun, Tang Ke-Jing, Cho Byoung Chul, Cheng Susanna, Popat Sanjay, Ono Akira, Lu Shun, Majem Margarita, Aguilar Andres, Del Rosario Garcia Campelo Maria, Hayashi Hidetoshi, Lee Kang-Yun, Lee Se-Hoon, Delmonte Angelo, Alatorre-Alexander Jorge, Richardson Gary, Santos Victor, Dooms Christophe, Sabari Joshua K, Shu Catherine A, Girard Nicolas, Mansfield Aaron S, Park Keunchil, Xia Yichuan, Bhattacharya Archan, Buyukkaramikli Nasuh, Perualila Nolen, Diels Joris, Acharya Sandip, Chandler Conor, Proskorovsky Irina, Dearden Lindsay, Wortman-Vayn Honeylet, Mahadevia Parthiv J, Knoblauch Roland E, Agrawal Trishala, Baig Mahadi, Felip Enriqueta
Аннотация
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.