TY - JOUR
T1 - Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer
AU - Levy, Benjamin P.
AU - Giaccone, Giuseppe
AU - Besse, Benjamin
AU - Felip, Enriqueta
AU - Garassino, Marina Chiara
AU - Domine Gomez, Manuel
AU - Garrido, Pilar
AU - Piperdi, Bilal
AU - Ponce-Aix, Santiago
AU - Menezes, Daniel
AU - MacBeth, Kyle J.
AU - Risueño, Alberto
AU - Slepetis, Ruta
AU - Wu, Xiaoling
AU - Fandi, Abderrahim
AU - Paz-Ares, Luis
N1 - Funding Information:
This study was funded by Celgene Corporation and Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Editorial assistance was provided by William Ho, PhD, MediTech Media, Ltd, funded by Celgene Corporation.BPL has received personal fees for medical advisory boards from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Lilly, Merck Sharp & Dohme, Novartis, Pfizer and Roche. GG has nothing to disclose. BB has received grants/research support from Celgene Corporation. EF received consultant fees for medical advisory boards from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, AbbVie and Merck. MCG received consultant fees for medical advisory boards and was part of the Speakers’ Bureaus for AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme and Roche. MDG has nothing to disclose. PG received honoraria or consultation fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer and Roche and was part of the Speakers’ Bureaus for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Guardant, Merck Sharp & Dohme, Novartis, Pfizer and Roche. BP is an employee of and has stock ownership with Merck Sharp & Dohme. SP-A has nothing to disclose. DM, KJM, AR, RS, XW and AF are employees of Celgene, the study sponsor and have stock ownership. KJM has a patent licenced (US9693987B2). LP-A has received honoraria or consultation fees from Roche, Lilly, Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, AstraZeneca, Amgen and Takeda.Medical writing assistance was provided by William Ho, PhD, MediTech Media, Ltd, funded by Celgene Corporation. All listed authors were fully responsible for all content and editorial decisions for this manuscript.
Funding Information:
This study was funded by Celgene Corporation and Merck Sharp & Dohme, Corp ., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Editorial assistance was provided by William Ho, PhD, MediTech Media, Ltd, funded by Celgene Corporation .
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/2
Y1 - 2019/2
N2 - Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
KW - Azacitidine
KW - CC-486
KW - Epigenetics
KW - Non-small cell lung cancer
KW - Pembrolizumab
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U2 - 10.1016/j.ejca.2018.11.028
DO - 10.1016/j.ejca.2018.11.028
M3 - Article
C2 - 30654297
AN - SCOPUS:85059857787
SN - 0959-8049
VL - 108
SP - 120
EP - 128
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -