Benjamin P Levy1, Giuseppe Giaccone2, Benjamin Besse3, Enriqueta Felip4, Marina Chiara Garassino5, Manuel Domine Gomez6, Pilar Garrido7, Bilal Piperdi8, Santiago Ponce-Aix9, Daniel Menezes10, Kyle J MacBeth10, Alberto Risueño11, Ruta Slepetis10, Xiaoling Wu10, Abderrahim Fandi10, Luis Paz-Ares12. 1. Johns Hopkins Sidney Kimmel Cancer Center, Washington, DC, USA. Electronic address: blevy11@jhmi.edu. 2. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. 3. Department of Cancer Medicine, Gustave Roussy, Villejuif and Paris-Sud University, Orsay, France. 4. Hospital University Vall d'Hebron, Barcelona, Spain. 5. Istituto Nazionale dei Tumori, Milan, Italy. 6. Instituto de Investigacion Sanitaria-Fundación Jimenez Diaz (IIS- FJD), Madrid, Spain. 7. IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain. 8. Merck & Co., Inc., Kenilworth, NJ, USA. 9. Hospital Universitario 12 de Octubre, Universidad Complutense, CNIO and CiberOnc, Madrid, Spain. 10. Celgene Corporation, Summit, NJ, USA. 11. Celgene Institute for Translational Research Europe, Seville, Spain. 12. Hospital Universitario 12 de Octubre, Universidad Complutense, CNIO and CiberOnc, Madrid, Spain. Electronic address: lpazaresr@seom.org.
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.
RCT Entities:
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: Anders Berglund; Matthew Mills; Ryan M Putney; Imène Hamaidi; James Mulé; Sungjune Kim Journal: J Clin Invest Date: 2020-02-03 Impact factor: 14.808
Authors: Haiying Cheng; Yiyu Zou; Chirag D Shah; Ni Fan; Tushar D Bhagat; Rasim Gucalp; Mimi Kim; Amit Verma; Bilal Piperdi; Simon D Spivack; Balazs Halmos; Roman Perez-Soler Journal: Lung Cancer Date: 2021-02-17 Impact factor: 5.705
Authors: Michael J Topper; Michelle Vaz; Kristen A Marrone; Julie R Brahmer; Stephen B Baylin Journal: Nat Rev Clin Oncol Date: 2019-09-23 Impact factor: 66.675