Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ pharmacology
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Disease-Free Survival
Female
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Neoplasm Metastasis
Pemetrexed
/ pharmacology
Platinum
/ pharmacology
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
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