Medline ® Abstract for Reference 4
of 'Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition'
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, CrinòL, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR
N Engl J Med. 2015;373(17):1627. Epub 2015 Sep 27.
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.).
From the Fox Chase Cancer Center, Philadelphia (H.B.); Hospital Universitario Virgen del Rocio, Seville (L.P.-A.), Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona (E.F.), and Hospital de Madrid, Norte Sanchinarro, Madrid (E.H.) - all in Spain; Vanderbilt-Ingram Cancer Center (L.H.), and Sarah Cannon Research Institute and Tennessee Oncology (D.R.S.) - both in Nashville; Thoraxklinik, Heidelberg University Hospital, Heidelberg (M.S.) and Robert-Bosch-Krankenhaus Stuttgart, Gerlingen (M.K.) - both in Germany; Duke University Medical Center, Durham, NC (N.E.R.); University of Washington, Seattle (L.Q.C.); University of Chicago Medicine and Biological Sciences, Chicago (E.E.V.); Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille (F.B.), Centre Léon Bérard, Lyon (J.F.), and Centre Hospitalier Universitaire de Rennes, Rennes (H.L.) - all in France; Instituto Nacional de Cancerologia, Mexico City (O.A.); Istituto Scientifico Rom