Assessing time to symptomatic progression, a patient-relevant efficacy endpoint, in the MARIPOSA study in non-small cell lung cancer
Recommended Citation
Nguyen D, Lee SH, Lu S, Girard N, Lin CC, Felip E, Aguilar A, Charoentum C, Cruz FM, Akamatsu H, Kowalyszyn R, Arslan C, Forster MD, Urban D, Misch D, Montes LVG, Gadgeel SM, Cruz-Correa M, Owen S, Schuette W, Sermon J, Kerßenboom R, Frosien M, Meißner J, Ord P, Ennis M, Fennema E, Sethi S, Bauml JM, Daksh M, Cho BC. Assessing Time to Symptomatic Progression, a Patient-Relevant Efficacy Endpoint, in the Mariposa Study in Non-Small Cell Lung Cancer. Eur J Cancer. 2026;245:116938.
Document Type
Article
Publication Date
9-9-2026
Publication Title
European journal of cancer (Oxford, England : 1990)
Keywords
Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Indoles, Disease Progression, Pyrimidines, Antineoplastic Combined Chemotherapy Protocols, Aniline Compounds, Female, Acrylamides, Quinolines, Time Factors, Male, Middle Aged, Progression-Free Survival, Aged, Patient Reported Outcome Measures, ErbB Receptors, Treatment Outcome
Abstract
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.
CONCLUSIONS: Amivantamab and lazertinib significantly delayed TTSP versus osimertinib. TTSP offers a clinician-validated measurement of disease-specific symptom worsening, capturing symptoms perceived by patients that prompt clinical action. TTSP is highly correlated with PFS and OS, providing complementary insights alongside traditional endpoints. TTSP enhances understanding of treatment benefit and supports informed clinical decision-making by integrating patient experience.
Medical Subject Headings
Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Indoles; Disease Progression; Pyrimidines; Antineoplastic Combined Chemotherapy Protocols; Aniline Compounds; Female; Acrylamides; Quinolines; Time Factors; Male; Middle Aged; Progression-Free Survival; Aged; Patient Reported Outcome Measures; ErbB Receptors; Treatment Outcome
PubMed ID
42492306
Volume
245
First Page
116938
Last Page
116938
