Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer

Benjamin P. Levy, Giuseppe Giaccone, Benjamin Besse, Enriqueta Felip, Marina Chiara Garassino, Manuel Domine Gomez, Pilar Garrido, Bilal Piperdi, Santiago Ponce-Aix, Daniel Menezes, Kyle J. MacBeth, Alberto Risueño, Ruta Slepetis, Xiaoling Wu, Abderrahim Fandi, Luis Paz-Ares

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)120-128
Number of pages9
JournalEuropean Journal of Cancer
Volume108
DOIs
StatePublished - Feb 2019

Keywords

  • Azacitidine
  • CC-486
  • Epigenetics
  • Non-small cell lung cancer
  • Pembrolizumab

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer'. Together they form a unique fingerprint.

  • Cite this

    Levy, B. P., Giaccone, G., Besse, B., Felip, E., Garassino, M. C., Domine Gomez, M., Garrido, P., Piperdi, B., Ponce-Aix, S., Menezes, D., MacBeth, K. J., Risueño, A., Slepetis, R., Wu, X., Fandi, A., & Paz-Ares, L. (2019). Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer. European Journal of Cancer, 108, 120-128. https://doi.org/10.1016/j.ejca.2018.11.028