Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer Journal Article
| Authors: | 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.; Kohlhaufl, M.; Arrieta, O.; Burgio, M. A.; Fayette, J.; Lena, H.; Poddubskaya, E.; Gerber, D. E.; Gettinger, S. N.; Rudin, C. M.; Rizvi, N.; Crino, L.; Blumenschein, G. R.; Antonia, S. J.; Dorange, C.; Harbison, C. T.; Finckenstein, F. G.; Brahmer, J. R. |
| Article Title: | Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer |
| 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 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.) |
| Keywords: | erlotinib; chemotherapy; safety; randomized controlled-trial; phase-iii trial; blockade; anti-pd-1 antibody |
| Journal Title: | New England Journal of Medicine |
| Volume: | 373 |
| Issue: | 17 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2015-10-22 |
| Start Page: | 1627 |
| End Page: | 1639 |
| Language: | English |
| ACCESSION: | WOS:000363317800008 |
| DOI: | 10.1056/NEJMoa1507643 |
| PROVIDER: | wos |
| PUBMED: | 26412456 |
| PMCID: | PMC5705936 |
| Notes: | Article -- Source: Wos |
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