title: Pembrolizumab for the treatment of non-small-cell lung cancer.
abstract: BACKGROUND
  We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit.
  
  
  METHODS
  We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review.
  
  
  RESULTS
  Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached.
  
  
  CONCLUSIONS
  Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab. (Funded by Merck; KEYNOTE-001 ClinicalTrials.gov number, NCT01295827.).
authors.affiliation: The authors' affiliations are listed in the Appendix.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Garon
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.forename: Rina
authors.initials: R
authors.lastname: Hui
authors.forename: Natasha
authors.initials: N
authors.lastname: Leighl
authors.forename: Ani S
authors.initials: AS
authors.lastname: Balmanoukian
authors.forename: Joseph Paul
authors.initials: JP
authors.lastname: Eder
authors.forename: Amita
authors.initials: A
authors.lastname: Patnaik
authors.forename: Charu
authors.initials: C
authors.lastname: Aggarwal
authors.forename: Matthew
authors.initials: M
authors.lastname: Gubens
authors.forename: Leora
authors.initials: L
authors.lastname: Horn
authors.forename: Enric
authors.initials: E
authors.lastname: Carcereny
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Hellmann
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Goldman
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Marisa
authors.initials: M
authors.lastname: Dolled-Filhart
authors.forename: Ruth Z
authors.initials: RZ
authors.lastname: Rutledge
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jared K
authors.initials: JK
authors.lastname: Lunceford
authors.forename: Reshma
authors.initials: R
authors.lastname: Rangwala
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Lubiniecki
authors.forename: Charlotte
authors.initials: C
authors.lastname: Roach
authors.forename: Kenneth
authors.initials: K
authors.lastname: Emancipator
authors.forename: Leena
authors.initials: L
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000032:analysis* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D016019:Survival Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D015415:Biomarkers; C582435:pembrolizumab