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.).
authors.affiliation: 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 Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Forlì-Cesena (M.A.B.), and Ospedale di Perugia, Perugia (L.C.) - both in Italy; N.N. Blokhin Russian Cancer Research Center, Moscow (E.P.); University of Texas Southwestern Medical Center, Dallas (D.E.G.); Yale Comprehensive Cancer Center, New Haven, CT (S.N.G.); Memorial Sloan Kettering Cancer Center, New York (C.M.R., N.R.); University of Texas M.D. Anderson Cancer Center, Houston (G.R.B.); H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (S.J.A.); Bristol-Myers Squibb, Princeton, NJ (C.D., C.T.H., F.G.F.); and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.R.B.).
authors.forename: Hossein
authors.initials: H
authors.lastname: Borghaei
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: Martin
authors.initials: M
authors.lastname: Steins
authors.forename: Neal E
authors.initials: NE
authors.lastname: Ready
authors.forename: Laura Q
authors.initials: LQ
authors.lastname: Chow
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.forename: Esther
authors.initials: E
authors.lastname: Holgado
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.forename: Martin
authors.initials: M
authors.lastname: Kohlhäufl
authors.forename: Oscar
authors.initials: O
authors.lastname: Arrieta
authors.forename: Marco Angelo
authors.initials: MA
authors.lastname: Burgio
authors.forename: Jérôme
authors.initials: J
authors.lastname: Fayette
authors.forename: Hervé
authors.initials: H
authors.lastname: Lena
authors.forename: Elena
authors.initials: E
authors.lastname: Poddubskaya
authors.forename: David E
authors.initials: DE
authors.lastname: Gerber
authors.forename: Scott N
authors.initials: SN
authors.lastname: Gettinger
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rudin
authors.forename: Naiyer
authors.initials: N
authors.lastname: Rizvi
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.forename: George R
authors.initials: GR
authors.lastname: Blumenschein
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Antonia
authors.forename: Cécile
authors.initials: C
authors.lastname: Dorange
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Harbison
authors.forename: Friedrich
authors.initials: F
authors.lastname: Graf Finckenstein
authors.forename: Julie R
authors.initials: JR
authors.lastname: Brahmer
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000077594:Nivolumab; D016019:Survival Analysis; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D043823:Taxoids; D000077143:Docetaxel; D000077594:Nivolumab