PMID- 29284010 OWN - NLM STAT- MEDLINE DCOM- 20180129 LR - 20220330 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 12 DP - 2017 TI - Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. PG - e0189848 LID - 10.1371/journal.pone.0189848 [doi] LID - e0189848 AB - BACKGROUND: Colorectal cancers (CRCs) expressing programmed death ligand 1 (PD-L1) have poor prognosis. In the multicohort KEYNOTE-028 trial, the anti-PD-1 antibody pembrolizumab was evaluated in 20 PD-L1-positive advanced solid tumors. Herein, we report results for the advanced CRC cohort. METHODS: Patients with advanced, treatment-resistant PD-L1-positive carcinoma of the colon or rectum were enrolled, regardless of microsatellite instability (MSI) status. Pembrolizumab 10 mg/kg was administered every 2 weeks for up to 2 years or until disease progression/unacceptable toxicity. Response was assessed every 8 weeks for the first 6 months and every 12 weeks thereafter. Primary end points were safety and overall response rate by investigator review per Response Evaluation Criteria in Solid Tumors version 1.1. Data cutoff was June 20, 2016. RESULTS: Of 137 patients with CRC and samples evaluable for PD-L1 expression, 33 (24%) had PD-L1-positive tumors, of which 23 were enrolled. Median follow-up was 5.3 months, and 8 patients (35%) reported treatment-related adverse events (AEs), most commonly fatigue (n = 3, 13%), stomatitis (n = 2, 9%), and asthenia (n = 2, 9%). One patient (4%) experienced grade 4 treatment-related increased blood bilirubin. No grade 3 AEs, discontinuations, or deaths were attributed to treatment. Most patients (n = 15, 65%) experienced progressive disease. One partial response occurred in a patient (4%) with MSI-high CRC. CONCLUSION: Pembrolizumab demonstrated a favorable safety profile in advanced PD-L1-positive CRC. Antitumor activity was observed in a single patient with MSI-high CRC, warranting further evaluation in this patient population. (Clinicaltrials.gov registration: NCT02054806). FAU - O'Neil, Bert H AU - O'Neil BH AUID- ORCID: 0000-0001-7032-7453 AD - Department of Hematology/Oncology, Indiana University Simon Cancer Center, Indianapolis, Indiana, United States of America. FAU - Wallmark, John M AU - Wallmark JM AD - Department of Hematology/Oncology, Maryland Hematology Oncology, Rockville, Maryland, United States of America. FAU - Lorente, David AU - Lorente D AD - Prostate Cancer Targeted Therapy Group, The Royal Marsden, Sutton, United Kingdom. FAU - Elez, Elena AU - Elez E AD - Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. FAU - Raimbourg, Judith AU - Raimbourg J AD - Department of Oncology Medical, Institut de Cancerologie de l'Ouest, Nantes, France. FAU - Gomez-Roca, Carlos AU - Gomez-Roca C AD - Department of Oncology Medical, Institut Claudius Regaud and IUCT-Oncopole, Toulouse, France. FAU - Ejadi, Samuel AU - Ejadi S AD - Department of Oncology, Scottsdale Healthcare, Virginia G. Piper Cancer Center, Scottsdale, Arizona, United States of America. FAU - Piha-Paul, Sarina A AU - Piha-Paul SA AD - Department of Investigational Clinical Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America. FAU - Stein, Mark N AU - Stein MN AD - Department of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America. FAU - Abdul Razak, Albiruni R AU - Abdul Razak AR AD - Clinical Cancer Research Unit, Princess Margaret Cancer Centre, Toronto, Canada. FAU - Dotti, Katia AU - Dotti K AD - Department of Medical Oncology, Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori, Milan, Italy. FAU - Santoro, Armando AU - Santoro A AD - Humanitas Cancer Center, Humanitas Research Hospital, Rozzano, Italy. FAU - Cohen, Roger B AU - Cohen RB AD - Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America. FAU - Gould, Marlena AU - Gould M AD - Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America. FAU - Saraf, Sanatan AU - Saraf S AD - Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America. FAU - Stein, Karen AU - Stein K AD - Department of Clinical Research, Merck & Co., Inc., Kenilworth, New Jersey, United States of America. FAU - Han, Sae-Won AU - Han SW AD - Division of Hematology and Medical Oncology, Seoul National University Hospital, Seoul, Republic of Korea. LA - eng SI - ClinicalTrials.gov/NCT02054806 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20171228 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use MH - Antineoplastic Agents, Immunological/adverse effects/*therapeutic use MH - B7-H1 Antigen/*immunology MH - Cohort Studies MH - Colorectal Neoplasms/*drug therapy MH - Female MH - Humans MH - Male MH - Middle Aged PMC - PMC5746232 COIS- Competing Interests: B H O'Neil disclosed travel, accommodations, and expenses from Amgen. D Lorente disclosed consultant or advisory role for Janssen Pharma and Sanofi Aventis; D Lorente also received travel, accommodations, and expenses from Janssen Pharma and Sanofi Aventis. J Raimbourg received honoraria from Bristol-Myers Squibb, Roche, and Boehringer Ingelheim; she also received travel, accomodations, and expenses from Roche, Pierre Fabre, and Novartis. C Gomez-Roca disclosed consultant or advisory role for Novartis, Erytech Pharma, Sanofi Aventis; he also received travel, accomodations, and expenses from Roche, Amgen, and Bristol-Myers Squibb. SA Piha-Paul disclosed research funding from GlaxoSmithKline, Puma Biotechnology, Inc., Novartis, Merck & Co., Inc., Medivation, Inc., Principia Biopharma Inc., AbbVie, XuanZhu Biopharma, Helix BioPharma Corp., and Incyte, Inc. MN Stein received research funding from Merck & Co., Inc., AbbVie, Janssen Pharma, Medivation/Astellas, Oncoceutics, Inc., Bavarian Nordic, and Abraxis BioScience. A Santoro disclosed consultant or advisory role for Takeda, Eli Lilly, Amgen, Bayer, and ArQule. R B Cohen disclosed research funding to his institution from Merck & Co., Inc. M Gould, S Saraf, and K Stein are currently (or were at the time the study was conducted) employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, who may own stock and/or hold stock options in Merck & Co., Inc. J Wallmark, E Elez, S Ejadi, AR Abdul Razak, K Dotti, and S-W Han claimed no conflicts of interest. There are no additional declarations from the authors relevant to this research relating to employment, consultancy, products in development, patents, or revenues from marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials, with the exception declared in the data availability statement. EDAT- 2017/12/29 06:00 MHDA- 2018/01/30 06:00 PMCR- 2017/12/28 CRDT- 2017/12/29 06:00 PHST- 2017/07/19 00:00 [received] PHST- 2017/10/30 00:00 [accepted] PHST- 2017/12/29 06:00 [entrez] PHST- 2017/12/29 06:00 [pubmed] PHST- 2018/01/30 06:00 [medline] PHST- 2017/12/28 00:00 [pmc-release] AID - PONE-D-17-23956 [pii] AID - 10.1371/journal.pone.0189848 [doi] PST - epublish SO - PLoS One. 2017 Dec 28;12(12):e0189848. doi: 10.1371/journal.pone.0189848. eCollection 2017.