Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer

作者：Danny Nguyen, Se‐Hoon Lee, Shun Lu, Nicolas Girard, Chien‐Chung Lin, Enriqueta Felip, Andrés Aguilar, Chaiyut Charoentum, Felipe Melo Cruz, Hiroaki Akamatsu, Rubén Dario Kowalyszyn, Cagatay Arslan, Martin D Forster, Damien Urban, Daniel Misch, Lizbett Vanessa Garcia Montes, Shirish M Gadgeel, Marcia Cruz-Correa, Scott Owen, Wolfgang Schuette, Jan Sermon, Ronja Kerßenboom, Markus Frosien, Janka Meißner, Priya Ord, Mariah Ennis, E. Fennema, Seema Sethi, Joshua Bauml, Mahesh Daksh, Byoung Chul Cho · 发表于：European Journal of Cancer · 年份：2026 · DOI：10.1016/j.ejca.2026.116938 · 研究领域：Lung Cancer Diagnosis and Treatment、Lung Cancer Treatments and Mutations、Lung Cancer Research Studies

INTRODUCTION: In the phase 3 randomized MARIPOSA study, amivantamab and lazertinib combination therapy demonstrated improved progression-free survival (PFS) and overall survival (OS) versus osimertinib in participants with previously untreated, epidermal growth factor receptor-mutated advanced non-small cell lung cancer. Time to symptomatic progression (TTSP) was introduced to assess clinical worsening and complement endpoints that investigate radiographic disease progression and patient-reported outcomes. TTSP provides an easily interpretable measure of disease-specific symptom worsening to further support patient experience. METHODS: In MARIPOSA, TTSP was quantitatively assessed as a secondary efficacy endpoint and defined as the time from randomization until participants experience disease-specific symptom worsening requiring a clinical intervention or treatment change, or death. To evaluate the impact of amivantamab and lazertinib on TTSP considering its established OS benefit against osimertinib, an exploratory analysis censoring death events was performed. RESULTS: At the final protocol-specified OS analysis (median follow up: 37.8 months), median TTSP was 43.6 months with amivantamab and lazertinib versus 29.3 months with osimertinib (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.57-0.83; p < 0.0001). Amivantamab and lazertinib reduced deaths following a TTSP event compared to osimertinib. A strong correlation between TTSP and PFS or OS was observed. CONCLUS...