Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer.
Adenocarcinoma of Lung
/ drug therapy
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Agents, Immunological
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Azacitidine
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Carcinoma, Squamous Cell
/ drug therapy
Female
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Progression-Free Survival
Survival Rate
Treatment Outcome
Azacitidine
CC-486
Epigenetics
Non-small cell lung cancer
Pembrolizumab
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
12
09
2018
revised:
15
11
2018
accepted:
23
11
2018
pubmed:
18
1
2019
medline:
10
5
2020
entrez:
18
1
2019
Statut:
ppublish
Résumé
Preclinical and early clinical studies suggest that combining epigenetic agents with checkpoint inhibitors can potentially improve outcomes in patients with previously treated advanced non-small cell lung cancer (NSCLC). This phase 2 trial examined second-line pembrolizumab + CC-486 (oral azacitidine) in patients with advanced NSCLC. Patients with one prior line of platinum-containing therapy were randomised in a ratio of 1:1 to CC-486 or placebo, on days 1-14, in combination with pembrolizumab on day 1 of a 21-day cycle. The primary end-point was progression-free survival (PFS). Key secondary end-points included overall survival (OS), overall response rate (ORR) and safety. Among 100 patients randomised (pembrolizumab + CC-486: 51; pembrolizumab + placebo: 49), most were male (57.0%), were white (87.0%) and had Eastern Cooperative Oncology Group performance status 1 (68.0%). No significant difference in PFS was observed between the pembrolizumab + CC-486 and pembrolizumab + placebo arms (median, 2.9 and 4.0 months, respectively; hazard ratio [HR], 1.374; 90% confidence interval [CI], 0.926-2.038; P = 0.1789). Median OS was 11.9 months versus not estimable (HR, 1.375; 90% CI, 0.830-2.276; P = 0.2968); ORR was 20% versus 14%. Median treatment duration was shorter (15.0 versus 24.1 weeks), and the number of cycles was lower (5.0 versus 7.0) with pembrolizumab + CC-486 versus pembrolizumab + placebo. No new safety signals for CC-486 or pembrolizumab were detected. Treatment-emergent adverse events were more common in the pembrolizumab + CC-486 arm, particularly gastrointestinal, potentially impacting treatment feasibility. No improvement in PFS was observed with pembrolizumab + CC-486 versus pembrolizumab + placebo. Decreased treatment exposure due to adverse events may have impacted efficacy with pembrolizumab + CC-486.
Identifiants
pubmed: 30654297
pii: S0959-8049(18)31535-1
doi: 10.1016/j.ejca.2018.11.028
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
pembrolizumab
DPT0O3T46P
Azacitidine
M801H13NRU
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
120-128Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 Elsevier Ltd. All rights reserved.