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 - 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 -