Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer.


Journal

Journal of clinical oncology : official journal of the American Society of Clinical Oncology
ISSN: 1527-7755
Titre abrégé: J Clin Oncol
Pays: United States
ID NLM: 8309333

Informations de publication

Date de publication:
10 05 2020
Historique:
pubmed: 10 3 2020
medline: 2 2 2021
entrez: 10 3 2020
Statut: ppublish

Résumé

In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680). Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis. As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups. First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.

Identifiants

pubmed: 32150489
doi: 10.1200/JCO.19.03136
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Pemetrexed 04Q9AIZ7NO
Platinum 49DFR088MY
pembrolizumab DPT0O3T46P

Banques de données

ClinicalTrials.gov
['NCT02578680']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1505-1517

Auteurs

Shirish Gadgeel (S)

Karmanos Cancer Institute, Detroit, MI.

Delvys Rodríguez-Abreu (D)

Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.

Giovanna Speranza (G)

Centre Integré de Cancérologie de la Montérégie, Hôpital Charles-Le Moyne, Greenfield Park, Quebec, Canada.

Emilio Esteban (E)

Hospital Universitario Central de Asturias, Oviedo, Spain.

Enriqueta Felip (E)

Vall d'Hebron University, Vall d'Hebron Institute of Oncology, Barcelona, Spain.

Manuel Dómine (M)

Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain.

Rina Hui (R)

Westmead Hospital and University of Sydney, Sydney, New South Wales, Australia.

Maximilian J Hochmair (MJ)

Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Vienna, Austria.

Philip Clingan (P)

Southern Medical Day Care Centre, Wollongong, New South Wales, Australia.

Steven F Powell (SF)

Sanford Health, Sioux Falls, SD.

Susanna Yee-Shan Cheng (SY)

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

Helge G Bischoff (HG)

Thoraxklinik, Heidelberg, Germany.

Nir Peled (N)

Soroka Medical Center, Ben-Gurion University, Beer Sheva, Israel.

Francesco Grossi (F)

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Ross R Jennens (RR)

Epworth Healthcare, Richmond, Victoria, Australia.

Martin Reck (M)

LungenClinic, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

Edward B Garon (EB)

David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA.

Silvia Novello (S)

Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria San Luigi, Orbassano, Italy.

Belén Rubio-Viqueira (B)

Hospital Universitario Quirónsalud Madrid, Madrid, Spain.

Michael Boyer (M)

Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.

Takayasu Kurata (T)

Kansai Medical University Hospital, Osaka, Japan.

Jhanelle E Gray (JE)

Moffitt Cancer Center, Tampa, FL.

Jing Yang (J)

Merck & Co, Kenilworth, NJ.

Tuba Bas (T)

Merck & Co, Kenilworth, NJ.

M Catherine Pietanza (MC)

Merck & Co, Kenilworth, NJ.

Marina C Garassino (MC)

Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori, Milan, Italy.

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Classifications MeSH