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

Overview

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.

authors

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

publication date

  • January 14, 2019

Research

keywords

  • Adenocarcinoma of Lung
  • Antineoplastic Combined Chemotherapy Protocols
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Squamous Cell
  • Lung Neoplasms

Identity

Scopus Document Identifier

  • 85059857787

Digital Object Identifier (DOI)

  • 10.1016/j.ejca.2018.11.028

PubMed ID

  • 30654297

Additional Document Info

volume

  • 108