title: Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.
abstract: BACKGROUND
  Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer.
  
  
  METHODS
  We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759.
  
  
  RESULTS
  Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7-22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2-4·8), and median duration of response was not reached (95% CI 8·31-not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7-10·9). 20 (17%) of 117 patients reported grade 3-4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease.
  
  
  CONCLUSIONS
  Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment.
  
  
  BACKGROUND
  Bristol-Myers Squibb.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address: nar2144@cumc.columbia.edu.
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.affiliation: Hôpital Larrey, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
authors.affiliation: L'Institut Gustave Roussy, Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Planchard
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Dy
authors.affiliation: H Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Antonia
authors.affiliation: Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
authors.affiliation: Centre Hospitalier Universitaire de Rennes, Rennes, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lena
authors.affiliation: Ospedale S Maria, Terni, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Minenza
authors.affiliation: Nouvel Hôpital Civil Chru de Strasbourg, Strasbourg, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Mennecier
authors.affiliation: The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.affiliation: Oncology Consultants, PA, Houston, TX, USA.
authors.forename: Luis T
authors.initials: LT
authors.lastname: Campos
authors.affiliation: University of California Davis Cancer Center, Sacramento, CA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
authors.affiliation: Mount Sinai Beth Israel Comprehensive Cancer Center, New York, NY, USA.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Levy
authors.affiliation: Lehigh Valley Hospital, Allentown, PA, USA.
authors.forename: Suresh G
authors.initials: SG
authors.lastname: Nair
authors.affiliation: Centre Hospitalier Universitaire de Caen, Caen, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.affiliation: Universitaetsklinik Koeln, Koeln, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
authors.affiliation: Hospices Civils de Lyon, Ch Lyon Sud, Pierre Benite, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Souquet
authors.affiliation: Ospedale Campo Di Marte, Lucca, Italy.
authors.forename: Editta
authors.initials: E
authors.lastname: Baldini
authors.affiliation: Istituto Toscano Tumori, Livorno, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.affiliation: Chi De Creteil, Creteil, France.
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.affiliation: University Hospitals of Cleveland, Cleveland, OH, USA.
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.affiliation: Providence Portland Medical Center, Portland, OR, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sanborn
authors.affiliation: University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Lopez-Chavez
authors.affiliation: Evangelische Lungenklinik Berlin, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grohe
authors.affiliation: Klinikum der Universitaet Muenchen-Innenstadt, German Center for Lung Research, Munich, Germany.
authors.forename: Rudolf M
authors.initials: RM
authors.lastname: Huber
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Harbison
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Baudelet
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lestini
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015897:Comorbidity; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab