Journal article
Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial
Clinical cancer research, Vol.28(12), pp.2547-2554
06/13/2022
DOI: 10.1158/1078-0432.CCR-21-3807
PMCID: PMC9784157
PMID: 35421228
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial
- Creators
- Gontran Verset - Université Libre de BruxellesIvan Borbath - UCLouvainMark Karwal - University of IowaChris Verslype - KU LeuvenHans Van Vlierberghe - Ghent University HospitalAdel Kardosh - Oregon Health & Science UniversityVittorina Zagonel - Istituto Oncologico VenetoPer Stal - Karolinska InstitutetDebashis Sarker - King's College LondonDaniel H Palmer - University of LiverpoolArndt Vogel - Medizinische Hochschule HannoverJulien Edeline - Centre Eugène MarquisStephane Cattan - Centre Hospitalier Universitaire de LilleMasatoshi Kudo - Kindai UniversityAnn-Lii Cheng - National Taiwan University HospitalSadahisa Ogasawara - Chiba UniversityBruno Daniele - Ospedale del Mare, Napoli, Italy.Stephen L Chan - Chinese University of Hong KongJennifer J Knox - Princess Margaret Cancer CentreShukui Qin - Nanjing University of Chinese MedicineAbby B Siegel - Merck & Co., Inc., Rahway, NJ, USA (United States)Michael Chisamore - Merck & Co., Inc., Rahway, NJ, USA (United States)Ken Hatogai - Merck & Co., Inc., Rahway, NJ, USA (United States)Anran Wang - Merck & Co., Inc., Rahway, NJ, USA (United States)Richard S Finn - Ronald Reagan UCLA Medical CenterAndrew X Zhu - Jiahui International Cancer Center, Jiahui International Hospital, Shanghai, China.
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.28(12), pp.2547-2554
- DOI
- 10.1158/1078-0432.CCR-21-3807
- PMID
- 35421228
- PMCID
- PMC9784157
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- DOI: 10.13039/100009947, name: Merck Sharp & Dohme Corp.; name: Merck & Co., Inc., Kenilworth, NJ
- Language
- English
- Date published
- 06/13/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359909002771
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