Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2023 Mar 1;41(7):1434-1443.
doi: 10.1200/JCO.22.00620. Epub 2022 Dec 1.

Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial

Shukui Qin  1 , Zhendong Chen  2 , Weijia Fang  3 , Zhenggang Ren  4 , Ruocai Xu  5 , Baek-Yeol Ryoo  6 , Zhiqiang Meng  7 , Yuxian Bai  8 , Xiaoming Chen  9   10 , Xiufeng Liu  1 , Juxiang Xiao  11 , Gwo Fuang Ho  12 , Yimin Mao  13 , Xin Wang  14 , Jieer Ying  15 , Jianfeng Li  16 , Wenyan Zhong  17 , Yu Zhou  17 , Abby B Siegel  18 , Chunyi Hao  19
Affiliations
Clinical Trial

Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial

Shukui Qin et al. J Clin Oncol. .

Abstract

Purpose: We evaluated the efficacy and safety of pembrolizumab in patients from Asia with previously treated advanced hepatocellular carcinoma (HCC).

Methods: In a double-blind, phase III trial, 453 patients with advanced HCC and progression during or after treatment with or intolerance to sorafenib or oxaliplatin-based chemotherapy were randomly assigned in a 2:1 ratio to receive pembrolizumab (200 mg) or placebo once every 3 weeks for ≤ 35 cycles plus best supportive care. The primary end point was overall survival (one-sided significance threshold, P = .0193 [final analysis]). Secondary end points included progression-free survival (PFS) and objective response rate (ORR; one-sided significance threshold, P = .0134 and .0091, respectively [second interim analysis]; RECIST version 1.1, by blinded independent central review).

Results: Median overall survival was longer in the pembrolizumab group than in the placebo group (14.6 v 13.0 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P = .0180). Median PFS was also longer in the pembrolizumab group than in the placebo group (2.6 v 2.3 months; hazard ratio for progression or death, 0.74; 95% CI, 0.60 to 0.92; P = .0032). ORR was greater in the pembrolizumab group (12.7% [95% CI, 9.1 to 17.0]) than in the placebo group (1.3% [95% CI, 0.2 to 4.6]; P < .0001). Treatment-related adverse events occurred in 66.9% of patients (grade 3, 12.0%; grade 4, 1.3%; grade 5, 1.0%) in the pembrolizumab group and 49.7% of patients (grade 3, 5.9%; grade 4, 0%; grade 5, 0%) in the placebo group.

Conclusion: In patients from Asia with previously treated advanced HCC, pembrolizumab significantly prolonged overall survival and PFS, and ORR was greater versus placebo.

Trial registration: ClinicalTrials.gov NCT03062358.

PubMed Disclaimer

Figures

FIG 1.
FIG 1.
CONSORT diagram.
FIG 2.
FIG 2.
Kaplan-Meier analysis of (A) OS at final analysis and (B) PFS at the second interim analysis. OS, overall survival; PFS, progression-free survival.
See this image and copyright information in PMC

Comment in

References

    1. World Health Organization : GLOBOCAN 2020 – Liver Cancer Factsheet. Geneva, World Health Organization, 2020
    1. Sung H, Ferlay J, Siegel RL, et al. : Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209-249, 2021 - PubMed
    1. Park JW, Chen M, Colombo M, et al. : Global patterns of hepatocellular carcinoma management from diagnosis to death: The BRIDGE Study. Liver Int 35:2155-2166, 2015 - PMC - PubMed
    1. Finn RS, Qin S, Ikeda M, et al. : Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382:1894-1905, 2020 - PubMed
    1. Ren Z, Xu J, Bai Y, et al. : Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): A randomised, open-label, phase 2-3 study. Lancet Oncol 22:977-990, 2021 - PubMed

Publication types

MeSH terms

Substances

Associated data