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Medline ® Abstract for Reference 10

of 'Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition'

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR, KEYNOTE-024 Investigators
N Engl J Med. 2016;375(19):1823. Epub 2016 Oct 8.
BACKGROUND: Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
METHODS: In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy. Crossover from the chemotherapy group to the pembrolizumab group was permitted in the event of disease progression. The primary end point, progression-free survival, was assessed by means of blinded, independent, central radiologic review. Secondary end points were overall survival, objective response rate, and safety.
RESULTS: Median progression-free survival was 10.3 months (95% confidence interval [CI], 6.7 to not reached) in the pembrolizumab group versus 6.0 months (95% CI, 4.2 to 6.2) in the chemotherapy group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.37 to 0.68; P<0.001). The estimated rate of overall survival at 6 months was 80.2% in the pembrolizumab group versus 72.4% in the chemotherapy group (hazard ratio for death, 0.60; 95% CI, 0.41 to 0.89; P=0.005). The response rate was higher in the pembrolizumab group than in the chemotherapy group (44.8% vs. 27.8%), the median duration of response was longer (not reached [range, 1.9+ to 14.5+ months]vs. 6.3 months [range, 2.1+ to 12.6+]), and treatment-related adverse events of any grade were less frequent (occurring in 73.4% vs. 90.0% of patients), as were grade 3, 4, or 5 treatment-related adverse events (26.6% vs. 53.3%).
CONCLUSIONS: In patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, pembrolizumab was associated with significantly longer progression-free and overall survival and with fewer adverse events than was platinum-based chemotherapy. (Funded by Merck; KEYNOTE-024 ClinicalTrials.gov number, NCT02142738 .).
From Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany (M.R.); Hospital Universitario Insular de Gran Canaria, Las Palmas, Spain (D.R.-A.); Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada (A.G.R.); Westmead Hospital and the University of Sydney, Sydney (R.H.), and Southern Medical Day Care Centre, Wollongong, NSW (A.T.) - both in Australia; Jász-Nagykun-Szolnok County Hospital, Szolnok (T.C.), and Országos Korányi TBCés Pulmonológiai Intézet, Budapest (A.F.) - both in Hungary; Meir Medical Center, Kfar-Saba (M.G.), and Davidoff Cancer Center, Tel Aviv University, Petah Tikva (N.P.) - both in Israel; St. James's Hospital and Cancer Trials Ireland, Dublin (S.C.); the Royal Marsden Hospital, Sutton, Surrey, United Kingdom (M.O.); MedStar Franklin Square Hospital (S.R.) and Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (J.R.B.) - both in Baltimore; Okayama University Hospita