Pembrolizumab Versus Placebo as second-line therapy in patients From Asia with advanced hepatocellular carcinoma: A randomized, double-blind, phase III trial

Authors

Shukui Qin
Zhendong Chen
Weijia Fang
Zhenggang Ren
Ruocai Xu
Baek-Yeol Ryoo
Zhiqiang Meng
Yuxian Bai
Xiaoming Chen
Xiufeng Liu
Juxiang Xiao
Gwo Fuang HoFollow
Yimin Mao
Xin Wang
Jieer Ying
Jianfeng Li
Wenyan Zhong
Yu Zhou
Abby B. Siegel
Chunyi Hao

Document Type

Article

Publication Date

3-1-2023

Abstract

We evaluated the efficacy and safety of pembrolizumab in patients from Asia with previously treated advanced hepatocellular carcinoma (HCC).METHODSIn 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).RESULTSMedian 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.CONCLUSIONIn patients from Asia with previously treated advanced HCC, pembrolizumab significantly prolonged overall survival and PFS, and ORR was greater versus placebo.

Keywords

Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy protocols, Carcinoma, Hepatocellular, Double-blind method, Humans, Liver neoplasms

Divisions

fac_med,oncology

Publication Title

Journal of Clinical Oncology

Volume

41

Issue

7

Publisher

American Society of Clinical Oncology

Publisher Location

TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA