TY - JOUR
T1 - Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma
T2 - Data from the Open-Label, Phase II KEYNOTE-224 Trial
AU - Verset, Gontran
AU - Borbath, Ivan
AU - Karwal, Mark
AU - Verslype, Chris
AU - Van Vlierberghe, Hans
AU - Kardosh, Adel
AU - Zagonel, Vittorina
AU - Stal, Per
AU - Sarker, Debashis
AU - Palmer, Daniel H.
AU - Vogel, Arndt
AU - Edeline, Julien
AU - Cattan, Stephane
AU - Kudo, Masatoshi
AU - Cheng, Ann Lii
AU - Ogasawara, Sadahisa
AU - Daniele, Bruno
AU - Chan, Stephen L.
AU - Knox, Jennifer J.
AU - Qin, Shukui
AU - Siegel, Abby B.
AU - Chisamore, Michael
AU - Hatogai, Ken
AU - Wang, Anran
AU - Finn, Richard S.
AU - Zhu, Andrew X.
N1 - Funding Information:
G. Verset reports grants from Terumo, Bayer, Roche, and Eisai outside the submitted work. I. Borbath reports other support from Ipsen, Roche, and Eisai; grants from Servier; and other support from Bayer outside the submitted work. M. Karwal reports grants from Merck during the conduct of the study; and personal fees from Eisai outside the submitted work. C. Verslype reports grants from Bayer and Ipsen; and personal fees from Roche outside the submitted work. H. Van Vlierberghe reports other support from Merck during the conduct of the study. A. Kardosh reports other support from OHSU during the conduct of the study. V. Zagonel reports personal fees from Bristol-Myers Squibb, MSD, Ipsen, and EISAI; personal fees and nonfinancial support from Bayer and Roche; and personal fees from Janssen outside the submitted work. P. Stal reports grants from MSD during the conduct of the study. D. Sarker reports personal fees from MSD during the conduct of the study; personal fees and nonfinancial support from Ipsen; personal fees from Bayer, Eisai, AstraZe-neca, Surface Oncology, Sirtex Medical, Roche, and AAA; nonfinancial support from MiNA Therapeutics and Medivir; and grants from UCB and Inspirata outside the submitted work. D.H. Palmer reports personal fees from MSD, Roche, and Boston Scientific; grants and personal fees from Bristol-Myers Squibb, Bayer, AstraZeneca, Sirtex Medical, and NuCana; and personal fees from Eisai outside the submitted work. A. Vogel reports personal fees from Roche, Bayer, Bristol-Myers Squibb, Eisai, AstraZeneca, Merck, Incyte, Ipsen, Pierre Fabre, MSD, Sirtex Medical, BTG, Servier, and Terumo; and personal fees from GlaxoSmithKline outside the submitted work. J. Edeline reports other support from MSD during the conduct of the study; personal fees from MSD, Roche, AstraZeneca, Ipsen, Bayer, and Eisai; and grants and personal fees from Bristol-Myers Squibb, BeiGene, and Boston Scientific outside the submitted work. S. Cattan reports personal fees from Bayer, Ipsen, Astra, Merck, and Roche during the conduct of the study; and personal fees from Roche outside the submitted work. M. Kudo reports personal fees from MSD during the conduct of the study; personal fees from Eli Lilly, Bayer, and Bristol-Myers Squibb; grants and personal fees from Eisai, EA Pharma, and Ono Pharmaceutical Co., Ltd.; grants from Roche, Gilead Sciences, Taiho Pharmaceutical, Sumitomo Dainippon Pharma, Takeda, Otsuka, and AbbVie; and grants and personal fees from Chugai outside the submitted work. A.L. Cheng reports personal fees from Bayer Healthcare, Eisai, Ono Pharmaceutical, AstraZeneca, Genentech/Roche, MSD, Ipsen Innovation, F. Hoffmann-La Roche Ltd., Bayer Yakuhin, Ltd., IQVIA, Amgen Taiwan, Chugai Pharmaceutical, and Bristol-Myers Squibb outside the submitted work. S. Ogasawara reports grants and personal fees from MSD during the conduct of the study; grants and personal fees from Bayer, Eisai, Eli Lilly, Chugai Pharmaceutical, and AstraZeneca; and personal fees from Takeda outside the submitted work. B. Daniele reports personal fees from MSD, AstraZeneca, Ipsen, Eisai, Roche, Amgen, Sanofi, Merck Serono, Lilly, and Bayer
Funding Information:
The authors thank the patients and their families and all investigators and site personnel; Scot W. Ebbinghaus, Olga Kuznetsova, and Leonid Dubrovsky from Merck & Co., Inc., Kenilworth, NJ, for their input and discussions on data analysis. Medical writing assistance was provided by Yue Liu and Ina Nikolaeva of Merck & Co., Inc., Kenilworth, NJ. This work was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. The funder had a role in study design, collection, analysis, and interpretation of data, and medical writing support. All authors had full access to the data and approved the final version of the manuscript for submission for publication.
Publisher Copyright:
© 2022 The Authors.
PY - 2022/6/15
Y1 - 2022/6/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-21-3807
DO - 10.1158/1078-0432.CCR-21-3807
M3 - Review article
C2 - 35421228
AN - SCOPUS:85131902610
SN - 1078-0432
VL - 28
SP - 2547
EP - 2554
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -