Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer
Leena GandhiFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Delvys Rodríguez‐AbreuFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Shirish M. GadgeelKarmanos Cancer Institute, DetroitEmilio EstebanFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Enriqueta FelipFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Flávia De AngelisFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Manuel DómineFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Philip R. ClinganFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Maximilian J. HochmairFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Steven PowellFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Susanna Y. ChengFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Helge BischoffFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Nir PeledFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Francesco GrossiFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Ross JennensFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Martin ReckFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Rina HuiFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Edward B. GaronFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Michael BoyerFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Belén Rubio‐ViqueiraFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Silvia NovelloFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Takayasu KurataFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Jhanelle E. GrayFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);John VidaFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Ziwen WeiFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Jing YangFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Harry RaftopoulosFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);M. Catherine PietanzaFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);Marina Chiara GarassinoFrom NYU Perlmutter Cancer Center, New York (L.G.); Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria (D.R.-A.), Hospital Universitario Central de Asturias, Oviedo (E.E.), Vall d’Hebron University, Vall d’Hebron Institute of Oncology, Barcelona (E.F.), and Fundación Jiménez Díaz (M.D.) and Hospital Universitario Quirón Madrid (B.R.-V.), Madrid — all in Spain; Karmanos Cancer Institute, Detroit (S.G.);
2018en
ABI
Annotatsiya
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 placebo-combination 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. (Funded by Merck; KEYNOTE-189 ClinicalTrials.gov number, NCT02578680 .).
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