First-line pembrolizumab versus investigator-choice chemotherapy for mismatch repair–deficient or microsatellite instability–high metastatic colore...

Date 29 June 2016
Event ESMO World Congress on Gastrointestinal Cancer 2016
Session ESMO World Congress on Gastrointestinal Cancer 2016 - Abstracts book
Presenter Diaz Luis
Citation Annals of Oncology (2016) 27 (2): 1-85. 10.1093/annonc/mdw199
Authors D. Luis1, L. Dung1, Y. Takayuki2, A. Thierry3, B. Johanna4, K. Minori5, Z. Yinghua5, K.S. Peter5, L. Bao5, J. Dirk6
  • 1Sidney Kimmel Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA, /
  • 2National Cancer Center Hospital East, Kashiwa, Japan, /
  • 3Saint Antoine Hospital, Paris, France, /
  • 4Sarah Cannon Research Institute and Tennessee Oncology, Nashville, Tennessee, USA, /
  • 5Merck & Co., Inc., Kenilworth, New Jersey, USA, /
  • 6National Center for Tumor Diseases, Heidelberg, Germany, /

Abstract

Approximately 5% of metastatic colorectal carcinomas (CRCs) are mismatch-repair (MMR) deficient, leading to high levels of microsatellite instability (MSI). CRCs with high MSI (MSI-H) contain abundant lymphocyte infiltrates and strong expression of immune checkpoints, including the programmed death 1 (PD-1) receptor and its ligand PD-L1. Pembrolizumab is a humanized monoclonal antibody against PD-1 designed to block the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby permitting activation of an antitumor immune response. In the phase 2 KEYNOTE-016 study, pembrolizumab provided an objective response rate (ORR) of 40% in patients with progressive MMR-deficient metastatic CRC vs 0% in patients with MMR-proficient CRC. KEYNOTE-177 (ClinicalTrials.gov, NCT02563002) is an international, randomized, open-label, phase 3 study designed to evaluate the efficacy and safety of pembrolizumab compared with standard-of-care (SOC) chemotherapy in the first-line setting for MMR-deficient or MSI-H metastatic CRC.