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Abstract Details
Updated efficacy and safety of KEYNOTE-224: a phase II study of pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib
Eur J Cancer. 2022 May;167:1-12. doi: 10.1016/j.ejca.2022.02.009.Epub 2022 Mar 29.
1Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka, Japan. Electronic address: m-kudo@med.kindai.ac.jp.
2University of California, 10833 Le Conte Avenue, Los Angeles, CA, USA. Electronic address: RFinn@mednet.ucla.edu.
3Centre Eugene Marquis, Avenue de la Bataille Flandres-Dunkerque, Rennes, France. Electronic address: j.edeline@rennes.unicancer.fr.
4Hôpital Huriez, 2, Oscar Lambret Avenue, Lille, France. Electronic address: stephane.cattan@chru-lille.fr.
5Chiba University Graduate School of Medicine, Inohana Campus 1-8-1, Inohana, Chuo-ku, Chiba, Japan. Electronic address: sadahisa@me.com.
6CR UK Liverpool Experimental Cancer Medicine Centre, 5 Pembroke Place, Liverpool, UK; Clatterbridge Cancer Centre, Liverpool, UK. Electronic address: Daniel.Palmer@liverpool.ac.uk.
11King's College London, Strand, London, UK. Electronic address: debashis.sarker@kcl.ac.uk.
12Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, Brussels, Belgium. Electronic address: Gontran.Verset@erasme.ulb.ac.be.
13State Key Laboratory of Oncology in South China, The Chinese University of Hong Kong, Shatin, LG, LKS Specialist Clinic (North Wing), Hong Kong, China. Electronic address: l_chan@clo.cuhk.edu.hk.
14Princess Margaret Cancer Centre and University of Toronto, 610 University Avenue, Toronto, Ontario, Canada. Electronic address: jennifer.knox@uhn.ca.
15Ospedale del Mare, Via Enrico Russo, Napoli, Italy. Electronic address: b.daniele@libero.it.
16University of Hong Kong, Queen Mary Hospital, Hong Kong, 102 Pok Fu Lam Rd, Hong Kong, China. Electronic address: tyaucc@hku.hk.
17Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, USA. Electronic address: egurary@gmail.com.
18Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, USA. Electronic address: abby.siegel@merck.com.
19Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, USA. Electronic address: jiang.dian.wang@merck.com.
20National Taiwan University Cancer Center, No. 57, Lane 155, Keelung 3rd Road, Taipei, Taiwan. Electronic address: alcheng@ntu.edu.tw.
21Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA, USA; Jiahui International Cancer Center, Jiahui Health, Shanghai, China. Electronic address: AZHU@mgh.harvard.edu.
Abstract
Objective: Pembrolizumab, a PD-1 inhibitor, demonstrated anti-tumour activity and tolerability in patients treated with sorafenib and with advanced hepatocellular carcinoma in KEYNOTE-224. Longer-term efficacy and safety after ∼2.5 years of additional follow-up are reported.
Patients and methods: Adults with confirmed hepatocellular carcinoma who experienced progression after or intolerance to sorafenib treatment received pembrolizumab 200 mg every 3 weeks for ≤35 cycles or until confirmed progression, unacceptable toxicity, withdrawal of consent or investigator decision. The primary end-point was objective response rate assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumours v1.1. The secondary end-points included duration of response, disease control rate, time to progression, progression-free survival, overall survival and adverse events.
Results: Efficacy and safety were assessed in 104 patients. The median time from first dose to data cutoff was 45.1 months (range, 41.3-49.3). Objective response rate was 18.3% (95% CI: 11.4-27.1), and median duration of response was 21.0 months (range, 3.1 to 39.5+). Disease control rate was 61.5%, and median time to progression was 4.8 months (95% CI: 3.9-7.0). Median progression-free survival was 4.9 months (95% CI: 3.5-6.7) and median overall survival was 13.2 months (95% CI: 9.7-15.3). Of 104 patients, 76 (73.1%) patients reported treatment-related adverse events; most were low grade in severity (grade 3-4, n = 26 [25.0%]; grade 5, n = 1 [1.0%]). Immune-mediated hepatitis occurred in 3 patients (all grade 3). No viral-induced hepatitis flares occurred.
Conclusions: After ∼2.5 years of additional follow-up, pembrolizumab continued to provide durable anti-tumour activity and no new safety concerns were identified.