Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Borghaei, Hossein D.O.; Paz-Ares, Luis M.D.; Horn, Leora M.D.; Spigel, David R. M.D.; Steins, Martin M.D., Ph.D.; Ready, Neal E. M.D., Ph.D.; Chow, Laura Q. M.D.; Vokes, Everett E. M.D.; Felip, Enriqueta M.D.; Holgado, Esther M.D.; Barlesi, Fabrice M.D., Ph.D.; Kohlhaufl, Martin M.D., Ph.D.; Arrieta, Oscar M.D.; Burgio, Marco Angelo M.D.; Fayette, Jerome M.D., Ph.D.; Lena, Herve M.D.; Poddubskaya, Elena M.D.; Gerber, David E. M.D.; Gettinger, Scott N. M.D.; Rudin, Charles M. M.D., Ph.D.; Rizvi, Naiyer M.D.; Crino, Lucio M.D.; Blumenschein, George R. Jr. M.D.; Antonia, Scott J. M.D., Ph.D.; Dorange, Cecile M.S.; Harbison, Christopher T. Ph.D.; Graf Finckenstein, Friedrich M.D.; Brahmer, Julie R. M.D.
[Article]
New England Journal of Medicine.
373(17):1627-1639, October 22, 2015.
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BACKGROUND: Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.
METHODS: In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.
RESULTS: Overall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab versus 39% (95% CI, 33 to 45) with docetaxel. With additional follow-up, the overall survival rate at 18 months was 39% (95% CI, 34 to 45) with nivolumab versus 23% (95% CI, 19 to 28) with docetaxel. The response rate was 19% with nivolumab versus 12% with docetaxel (P=0.02). Although progression-free survival did not favor nivolumab over docetaxel (median, 2.3 months and 4.2 months, respectively), the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel (19% and 8%, respectively). Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (>=1%, >=5%, and >=10%) of the PD-1 ligand. Treatment-related adverse events of grade 3 or 4 were reported in 10% of the patients in the nivolumab group, as compared with 54% of those in the docetaxel group.
CONCLUSIONS: Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy, overall survival was longer with nivolumab than with docetaxel. (Funded by Bristol-Myers Squibb; CheckMate 057 ClinicalTrials.gov number, NCT01673867.)
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