Abstract | BACKGROUND: METHODS: 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<0.001). The objective response rate was 45.3% with nivolumab plus ipilimumab and 26.9% with chemotherapy. The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups, including patients with a PD-L1 expression level of at least 1% and those with a level of less than 1%. The rate of grade 3 or 4 treatment-related adverse events was 31.2% with nivolumab plus ipilimumab and 36.1% with chemotherapy. ical; CheckMate 227 ClinicalTrials.gov number, NCT02477826 .). CONCLUSIONS: Progression-free survival was significantly longer with first-line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden, irrespective of PD-L1 expression level. The results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection. (Funded by Bristol-Myers Squibb and Ono Pharmaceut
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Authors | Matthew D Hellmann, Tudor-Eliade Ciuleanu, Adam Pluzanski, Jong Seok Lee, Gregory A Otterson, Clarisse Audigier-Valette, Elisa Minenza, Helena Linardou, Sjaak Burgers, Pamela Salman, Hossein Borghaei, Suresh S Ramalingam, Julie Brahmer, Martin Reck, Kenneth J O'Byrne, William J Geese, George Green, Han Chang, Joseph Szustakowski, Prabhu Bhagavatheeswaran, Diane Healey, Yali Fu, Faith Nathan, Luis Paz-Ares |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 378
Issue 22
Pg. 2093-2104
(May 31 2018)
ISSN: 1533-4406 [Electronic] United States |
PMID | 29658845
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- B7-H1 Antigen
- Biomarkers, Tumor
- CD274 protein, human
- Ipilimumab
- Nivolumab
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal
(administration & dosage, adverse effects)
- Antineoplastic Agents, Immunological
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- B7-H1 Antigen
(genetics, metabolism)
- Biomarkers, Tumor
- Carcinoma, Non-Small-Cell Lung
(drug therapy, genetics)
- Disease-Free Survival
- Female
- Humans
- Ipilimumab
(administration & dosage, adverse effects)
- Kaplan-Meier Estimate
- Lung Neoplasms
(drug therapy, genetics)
- Male
- Middle Aged
- Mutation
- Neoplasm Staging
- Nivolumab
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