Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer

被引:5090
作者
Gandhi, L. [1 ]
Rodriguez-Abreu, D. [2 ]
Gadgeel, S. [7 ]
Esteban, E. [3 ]
Felip, E. [4 ]
De Angelis, F. [8 ]
Domine, M. [5 ]
Clingan, P. [10 ]
Hochmair, M. J. [15 ]
Powell, S. F. [16 ]
Cheng, S. Y. -S. [9 ]
Bischoff, H. G. [17 ]
Peled, N. [19 ]
Grossi, F. [20 ]
Jennens, R. R. [11 ]
Reck, M. [18 ]
Hui, R. [12 ,13 ]
Garon, E. B. [23 ]
Boyer, M. [14 ]
Rubio-Viqueira, B. [6 ]
Novello, S. [21 ]
Kurata, T. [24 ]
Gray, J. E. [25 ]
Vida, J. [26 ]
Wei, Z. [26 ]
Yang, J. [26 ]
Raftopoulos, H. [26 ]
Pietanza, M. C. [26 ]
Garassino, M. C. [22 ]
机构
[1] NYU, Perlmutter Canc Ctr, New York, NY USA
[2] Univ Las Palmas Gran Canaria, Univ Insular Maternoinfantil Gran Canaria, Complejo Hosp, Las Palmas Gran Canaria, Spain
[3] Hosp Univ Cent Asturias, Oviedo, Spain
[4] Vall dHebron Univ, Vall dHebron Inst Oncol, Barcelona, Spain
[5] Fdn Jimenez Diaz, Madrid, Spain
[6] Hosp Univ Quiron Madrid, Madrid, Spain
[7] Karmanos Canc Inst, Detroit, MI USA
[8] Monteregie Ctr, Integrated Hlth & Social Serv Ctr, Greenfield Pk, PQ, Canada
[9] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada
[10] Southern Med Day Care Ctr, Wollongong, NSW, Australia
[11] Epworth Healthcare, Richmond, Vic, Australia
[12] Westmead Hosp, Sydney, NSW, Australia
[13] Univ Sydney, Sydney, NSW, Australia
[14] Chris OBrien Lifehouse, Camperdown, NSW, Australia
[15] Otto Wagner Hosp, Vienna, Austria
[16] Sanford Hlth, Sioux Falls, SD USA
[17] Thoraxklin, Heidelberg, Germany
[18] German Ctr Lung Res, Airway Res Ctr North, Lungen Clin, Grosshansdorf, Germany
[19] Tel Aviv Univ, Davidoff Canc Ctr, Petah Tiqwa, Israel
[20] Osped Policlin San Martino, Genoa, Italy
[21] Univ San Luigi, Univ Turin, Azienda Osped, Orbassano, Italy
[22] Fdn IRCCS Ist Nazl Tumori, Milan, Italy
[23] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA
[24] Kansai Med Univ Hosp, Osaka, Japan
[25] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA
[26] Merck, Kenilworth, NJ USA
关键词
RANDOMIZED CONTROLLED-TRIAL; PEMETREXED PLUS; OPEN-LABEL; INDUCTION TREATMENT; PHASE-III; DOCETAXEL; CISPLATIN; NIVOLUMAB; 1ST-LINE; THERAPY;
D O I
10.1056/NEJMoa1801005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial. METHODS In this double-blind, phase 3 trial, we randomly assigned (in a 2: 1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy. Crossover to pembrolizumab monotherapy was permitted among the patients in the placebo-combination group who had verified disease progression. The primary end points were overall survival and progression-free survival, as assessed by blinded, independent central radiologic review. RESULTS After a median follow-up of 10.5 months, the estimated rate of overall survival at 12 months was 69.2% (95% confidence interval [CI], 64.1 to 73.8) in the pembrolizumab-combination group versus 49.4% (95% CI, 42.1 to 56.2) in the placebocombination group (hazard ratio for death, 0.49; 95% CI, 0.38 to 0.64; P< 0.001). Improvement in overall survival was seen across all PD-L1 categories that were evaluated. Median progression-free survival was 8.8 months (95% CI, 7.6 to 9.2) in the pembrolizumab-combination group and 4.9 months (95% CI, 4.7 to 5.5) in the placebo-combination group (hazard ratio for disease progression or death, 0.52; 95% CI, 0.43 to 0.64; P< 0.001). Adverse events of grade 3 or higher occurred in 67.2% of the patients in the pembrolizumab-combination group and in 65.8% of those in the placebo-combination group. CONCLUSIONS In patients with previously untreated metastatic nonsquamous NSCLC without EGFR or ALK mutations, the addition of pembrolizumab to standard chemotherapy of pemetrexed and a platinum-based drug resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.
引用
收藏
页码:2078 / 2092
页数:15
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