Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer

H. Borghaei, L. Paz-Ares, L. Horn, D. R. Spigel, M. Steins, N. E. Ready, L. Q. Chow, E. E. Vokes, E. Felip, E. Holgado, F. Barlesi, M. Kohlhufl, O. Arrieta, M. A. Burgio, J. Fayette, H. Lena, E. Poddubskaya, D. E. Gerber, S. N. Gettinger, C. M. RudinN. Rizvi, L. Crina, G. R. Blumenschein, S. J. Antonia, C. Dorange, C. T. Harbison, F. Graf Finckenstein, J. R. Brahmer

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4154 Scopus citations

Abstract

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 followup, 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.).

Original languageEnglish (US)
Pages (from-to)1627-1639
Number of pages13
JournalNew England Journal of Medicine
Volume373
Issue number17
DOIs
StatePublished - Oct 22 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., Barlesi, F., Kohlhufl, M., Arrieta, O., Burgio, M. A., Fayette, J., Lena, H., Poddubskaya, E., Gerber, D. E., Gettinger, S. N., ... Brahmer, J. R. (2015). Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. New England Journal of Medicine, 373(17), 1627-1639. https://doi.org/10.1056/NEJMoa1507643