Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial
Abstract
Background Immune checkpoint blockade therapy has shown promising results in patients with advanced hepatocellular carcinoma. We aimed to assess the efficacy and safety of pembrolizumab in this patient population. Methods KEYNOTE-224 is a non-randomised, multicentre, open-label, phase 2 trial that is set in 47 medical centres and hospitals across ten countries. Eligible patients had pathologically confirmed hepatocellular carcinoma; had previously been treated with sorafenib and were either intolerant to this treatment or showed radiographic progression of their disease after treatment; an Eastern Cooperative Oncology Group performance status of 0-1; adequate organ function, and were Child-Pugh class A. Participants received 200 mg pembrolizumab intravenously every 3 weeks for about 2 years or until disease progression, unacceptable toxicity, patient withdrawal, or investigator decision. The primary endpoint was objective response, defined as the proportion of patients with complete or partial response in all patients who received at least one dose of pembrolizumab, which was radiologically confirmed by use of the Response Evaluation Criteria in Solid Tumors version 1.1 by central review. Safety was also assessed in all treated patients. This trial is ongoing but closed to enrolment and is registered with ClinicalTrials.gov number NCT02702414. Findings Between June 7, 2016, and Feb 9, 2017, we screened 169 patients with advanced hepatocellular carcinoma, of whom 104 eligible…
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The combination of anti-PD-1 and lenvatinib raises the HCC patient response rate from 17% with anti-PD-1 alone to 45%.
“The combination of anti-PD-1 and lenvatinib, a multi-target tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptors, raises the HCC patient response rate from 17% with anti-PD-1 alone to 45%.”
From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [10]
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- Authors
- Zhu, A. X., Finn, R. S., Edeline, J., Cattan, S., Ogasawara, S., Palmer, D., Verslype, C., Zagonel, V., Fartoux, L., Vogel, A., Sarker, D., Verset, G., Chan, S. L., Knox, J., Daniele, B., Webber, A. L., Ebbinghaus, S. W., Ma, J., Siegel, A. B., Cheng, A.-L., Kudo, M., Alistar, A., Asselah, J., Blanc, J.-F., Borbath, I., Cannon, T., Chung, K., Cohn, A., Cosgrove, D. P., Damjanov, N., Gupta, M., Karino, Y., Karwal, M., Kaubisch, A., Kelley, R., Van Laethem, J.-L., Larson, T., Lee, J., Li, D., Manhas, A., Manji, G. A., Numata, K., Parsons, B., Paulson, A. S., Pinto, C., Ramirez, R., Ratnam, S., Rizell, M., Rosmorduc, O., Sada, Y., Sasaki, Y., Stal, P. I., Strasser, S., Trojan, J., Vaccaro, G., Van Vlierberghe, H., Weiss, A., Weiss, K.-H., & Yamashita, T.
- Affiliations
- Harvard University (US)
- University of California, Los Angeles (US)
- Centre Eugène Marquis (FR)
- Chiba University (JP)
- University of Liverpool (GB)
- Universitair Ziekenhuis Leuven (BE)
- Istituto Oncologico Veneto (IT)
- Medizinische Hochschule Hannover (DE)
- King's College Hospital (GB)
- Erasmus Hospital (BE)
- Chinese University of Hong Kong (HK)
- University of Toronto (CA)
- Azienda Ospedaliera G.Rummo (IT)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- National Taiwan University Hospital (TW)
- Kindai University (JP)
- Corresponding author
- Zhu, Andrew X
- ORCID
- Zhu, Andrew X
- Finn, Richard S
- Edeline, Julien
- Ogasawara, Sadahisa
- Palmer, Daniel
- Verslype, Chris
- Zagonel, Vittorina
- Vogel, Arndt
- Sarker, Debashis
- Verset, Gontran
- Chan, Stephen L
- Knox, Jennifer
- Daniele, Bruno
- Webber, Andrea L
- Ma, Junshui
- Siegel, Abby B
- Cheng, Ann-Lii
- Kudo, Masatoshi
- Alistar, Angela
- Asselah, Jamil
- Borbath, Ivan
- Cannon, Timothy
- Chung, Ki
- Cosgrove, David P
- Damjanov, Nevena
- Karwal, Mark
- Kaubisch, Andreas
- Kelley, Robin
- Larson, Timothy
- Lee, James
- Li, Daneng
- Manji, Gulam Abbas
- Numata, Kazushi
- Paulson, Andrew S.
- Pinto, Carmine
- Ramirez, Robert
- Rizell, Magnus
- Rosmorduc, Olivier
- Sada, Yvonne
- Sasaki, Yutaka
- Stal, Per I
- Strasser, Simone
- Vaccaro, Gina
- Yamashita, Tatsuya
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 19
- Issue
- 7
- Pages
- 940-952
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W2805592007
- Cited by
- 2,479
- References
- 5
- Citations by year
- 2026: 89 · 2025: 196 · 2024: 324 · 2023: 331 · 2022: 416 · 2021: 468 · 2020: 385 · 2019: 229 · 2018: 39 · 2016: 1
- FWCI
- 175.94
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-09-01)
- Open access
- closed
- Licence
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- Merck
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- pembrolizumab, hepatocellular carcinoma, immune checkpoint blockade, PD-1 inhibitors, sorafenib-refractory disease, objective response, treatment-related adverse events, immunotherapy, advanced liver cancer, treatment efficacy and safety, progression-free survival, overall survival, Child-Pugh score, treatment intolerance
- MeSH terms
- Sorafenib, Aged, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Carcinoma, Hepatocellular, Humans, Infusions, Intravenous, Liver Neoplasms, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prognosis, Remission Induction, Survival Rate, Disease-Free Survival, Internationality, Antibodies, Monoclonal, Humanized
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