Format

Send to

Choose Destination
N Engl J Med. 2018 Nov 22;379(21):2040-2051. doi: 10.1056/NEJMoa1810865. Epub 2018 Sep 25.

Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer.

Collaborators (145)

Ben Houghton B, Hui R, Jennens R, Aucoin N, Castonguay V, Robinson A, Roy J, Snow S, Speranza G, De Angelis F, Cao L, Gao H, Guo Y, Han Z, Hu C, Hu J, Huang M, Li X, Liu J, Ma Z, Sun H, Wang D, Wang Z, Wu L, Yu S, Zhang H, Zhang L, Zhou J, Corre R, Cousin S, Doucet L, Dourthe LM, Hiret S, Moro-Sibilot D, Quantin X, Scherpereel A, Thiberville L, Engel-Riedel W, Gruening W, Kollmeier J, Kokowski K, Spaeth-Schwalbe E, Balint B, Horvath I, Medgyasszay B, Tehenes S, D’Argento E, Berardi R, Gianni L, Minotti V, Rocco D, Soto Parra H, Akamatsu H, Aoe K, Atagi S, Fukuhara T, Hirashima T, Horinouchi H, Hosomi Y, Ichiki M, Imamura F, Kaji R, Kasahara K, Kishi K, Kubota K, Kurata T, Nakahara Y, Nishio M, Nogami N, Ohashi K, Okada M, Okamoto I, Saka H, Satouchi M, Takahashi T, Tanaka H, Tokito T, Udagawa H, Yokoyama T, Macedo-Perez E, de la Mora Jimenez E, Biesma B, Custers F, van den Heuvel MM, Kalinka-Warzoch E, Karaszewska B, Ramlau R, Kuzina L, Laktionov K, Mukhametshina G, Vladimirov V, Kang JH, Kim BS, Lee GW, Lee SS, Min YJ, Campos B, Felip E, Majem M, Massuti B, Ortega A, Provencio M, Trigo J, Dechaphunkul A, Korphaisarn K, Prasongsook N, Reungwetwattana T, Sriuranpong V, Cicin I, Erman M, Gunduz S, Harputluoglu H, Ozkan M, Oztop I, Turna H, Yavuz S, Costin D, Dragnev K, Duvivier H, Garon EB, Gerstner G, Graham M, Gralla R, Guarino MJ, Hattersley-Anderes E, Jaslowski A, Jotte R, Kendall SD, Kloecker G, Mekhail T, Mohebtash M, Parchman A, Rao SB, Reddy S, Robert F, Rybkin II, Santos E, Saylors G, Sleckman BG, Socoteanu M, Stampleman L, Stevenson J, Walsh WV, Waterhouse D, Wrangle J.

Author information

1
From Hospital Universitario 12 de Octubre, Spanish National Cancer Research Center, Universidad Complutense and Ciberonc, Madrid (L.P.-A.), and Hospital Universitario Virgen Macarena, Seville (D.V.) - both in Spain; Leningrad Regional Clinical Hospital, St. Petersburg, Russia (A.L.); Wollongong Oncology and Wollongong Private Hospital, Wollongong, NSW, Australia (A.T.); Istanbul Medeniyet University Hospital, Istanbul (M.G.), and Ankara University, Ankara (F.Ç.Ş.) - both in Turkey; Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France (J.M.); Universitätsklinikum Tübingen, Tübingen, Germany (B. Hermes); Jász-Nagykun-Szolnok County Hospital, Szolnok (T.C.), and Országos Korányi TBC és Pulmonológiai Intézet, Budapest (A.F.) - both in Hungary; Oncology Center, Medica Sur Hospital, Mexico City (J.R.-C.); Humber River Regional Hospital, Toronto (J.W.); Sendai Kousei Hospital, Sendai (S.S.), and the Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheong-ju, South Korea (K.H.L.); Jilin Cancer Hospital, Changchun, China (Y.C.); University of Turin, Orbassano, Italy (S.N.); Montefiore Medical Center-Albert Einstein College of Medicine, New York (B. Halmos); Merck, Kenilworth, NJ (X.L., G.M.L., B.P.); and the Maria Skłodowska-Curie Institute of Oncology, Warsaw, Poland (D.M.K.).

Abstract

BACKGROUND:

Standard first-line therapy for metastatic, squamous non-small-cell lung cancer (NSCLC) is platinum-based chemotherapy or pembrolizumab (for patients with programmed death ligand 1 [PD-L1] expression on ≥50% of tumor cells). More recently, pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC.

METHODS:

In this double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, 559 patients with untreated metastatic, squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]-paclitaxel for the first 4 cycles. Primary end points were overall survival and progression-free survival.

RESULTS:

After a median follow-up of 7.8 months, the median overall survival was 15.9 months (95% confidence interval [CI], 13.2 to not reached) in the pembrolizumab-combination group and 11.3 months (95% CI, 9.5 to 14.8) in the placebo-combination group (hazard ratio for death, 0.64; 95% CI, 0.49 to 0.85; P<0.001). The overall survival benefit was consistent regardless of the level of PD-L1 expression. The median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001). Adverse events of grade 3 or higher occurred in 69.8% of the patients in the pembrolizumab-combination group and in 68.2% of the patients in the placebo-combination group. Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab-combination group than in the placebo-combination group (13.3% vs. 6.4%).

CONCLUSIONS:

In patients with previously untreated metastatic, squamous NSCLC, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by Merck Sharp & Dohme; KEYNOTE-407 ClinicalTrials.gov number, NCT02775435 .).

PMID:
30280635
DOI:
10.1056/NEJMoa1810865
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Atypon Icon for University of Turin Instituional Repository AperTO
Loading ...
Support Center