1. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden
- Author
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Joseph D. Szustakowski, Prabhu Bhagavatheeswaran, Adam Pluzanski, Hossein Borghaei, George Green, Yali Fu, Julie R. Brahmer, Clarisse Audigier-Valette, Kenneth J. O'Byrne, Jong-Seok Lee, Pamela Salman, Luis Paz-Ares, William J. Geese, Diane Healey, Helena Linardou, Sjaak Burgers, Elisa Minenza, Martin Reck, Matthew D. Hellmann, Han Chang, Gregory A. Otterson, F. E. Nathan, Suresh S. Ramalingam, and Tudor-Eliade Ciuleanu
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Ipilimumab ,Kaplan-Meier Estimate ,Article ,B7-H1 Antigen ,Disease-Free Survival ,law.invention ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Randomized controlled trial ,law ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,Carcinoma ,Humans ,Medicine ,Lung cancer ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Chemotherapy ,business.industry ,Antibodies, Monoclonal ,General Medicine ,Middle Aged ,medicine.disease ,Clinical trial ,Nivolumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,Potential biomarkers ,Mutation ,Female ,business ,medicine.drug - Abstract
BACKGROUND: Nivolumab plus ipilimumab showed promising efficacy for the treatment of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (≥10 mutations per megabase). METHODS: We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy. Those with a level of tumor programmed death ligand 1 (PD-L1) expression of at least 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy; those with a tumor PD-L1 expression level of less than 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. Tumor mutational burden was determined by the FoundationOne CDx assay. RESULTS: Progression-free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy. The 1-year progression-free survival rate was 42.6% with nivolumab plus ipilimumab versus 13.2% with chemotherapy, and the median progression-free survival was 7.2 months (95% confidence interval [CI], 5.5 to 13.2) versus 5.5 months (95% CI, 4.4 to 5.8) (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41 to 0.81; P
- Published
- 2018