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Abstract Details
Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial
Clin Cancer Res. 2022 Jun 13;28(12):2547-2554.doi: 10.1158/1078-0432.CCR-21-3807
1Gastrointestinal Oncology Unit, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
2Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium.
3University of Iowa, Iowa City, Iowa.
4Digestive Oncology, Department of Oncology, University Hospital Leuven, Belgium.
5Ghent University, Ghent, Belgium.
6Oregon Health & Science University, Knight Cancer Institute, Portland, Oregon.
7Oncology Unit 1, Istituto Oncologico Veneto, IOV, IRCCS, Padua, Italy.
8Karolinska Institutet, Stockholm, Sweden.
9School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.
10Cancer Research UK Liverpool Experimental Cancer Medicine Centre, University of Liverpool, Liverpool, United Kingdom.
11Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule, Hannover, Germany.
12Department of Medical Oncology, Centre Eugène Marquis, Rennes, France.
13Department of Medical Oncology and Gastroenterology, Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
14Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
15Department of Medical Oncology, National Taiwan University Cancer Center, and Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
16Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
17Oncology Unit, Ospedale del Mare, Napoli, Italy.
18Department of Clinical Oncology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong.
19Department of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
20Cancer Centre of Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China.
21Merck & Co., Inc., Kenilworth, New Jersey.
22Department of Medicine, University of California, Los Angeles, California.
23Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts.
24Jiahui International Cancer Center, Jiahui Health, Shanghai, China
#Contributed equally.
Abstract
Purpose: KEYNOTE-224 cohort 1 demonstrated that pembrolizumab was efficacious and tolerable in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. We report results from KEYNOTE-224 (NCT02702414) cohort 2, which enrolled patients with advanced HCC and no prior systemic therapy.
Patients and methods: KEYNOTE-224 was an open-label, multicountry phase II trial. Eligible patients in cohort 2 had advanced HCC not amenable or refractory to locoregional therapy and not previously treated with systemic therapy. Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤2 years. Primary endpoint was objective response rate (ORR) by central imaging review per RECIST v1.1. Secondary endpoints included duration of response (DOR), disease control rate (DCR), time to progression (TTP), progression-free survival (PFS), overall survival (OS), and safety/tolerability.
Results: Between September 4, 2018, and February 20, 2019, 51 patients were allocated in cohort 2. The median time from the first dose to data cutoff (January 19, 2021) was 27 months (range, 23-29). ORR was 16% [95% confidence interval (CI), 7-29] and was similar across key subgroups. Median DOR was 16 months (range, 3-24+), and DCR was 57%. The median PFS was 4 months (95% CI, 2-8), and median TTP was 4 months (95% CI, 3-9). Median OS was 17 months (95% CI, 8-23). Grade ≥3 treatment-related adverse events occurred in 16% of patients.
Conclusions: In patients with advanced HCC with no prior systemic therapy, pembrolizumab provided durable antitumor activity, promising OS, and had a safety profile consistent with previous observations. These findings support further evaluation of pembrolizumab-based regimens for HCC.