TY - JOUR
T1 - Tislelizumab in Patients with Previously Treated Advanced Hepatocellular Carcinoma (RATIONALE-208)
T2 - A Multicenter, Non-Randomized, Open-Label, Phase 2 Trial
AU - Ren, Zhenggang
AU - Ducreux, Michel
AU - Abou-Alfa, Ghassan K.
AU - Merle, Philippe
AU - Fang, Weijia
AU - Edeline, Julien
AU - Li, Zhiwei
AU - Wu, Lihua
AU - Assenat, Eric
AU - Hu, Sheng
AU - Rimassa, Lorenza
AU - Zhang, Tao
AU - Blanc, Jean Frederic
AU - Pan, Hongming
AU - Ross, Paul
AU - Yen, Chia Jui
AU - Tran, Albert
AU - Shao, Guoliang
AU - Bouattour, Mohamed
AU - Chen, Yajin
AU - Meyer, Tim
AU - Hou, Jinlin
AU - Tougeron, David
AU - Bai, Yuxian
AU - Hou, Ming Mo
AU - Meng, Zhiqiang
AU - Wu, John
AU - Li, Vincent
AU - Chica-Duque, Sandra
AU - Cheng, Ann Lii
N1 - Publisher Copyright:
© 2022 Authors
PY - 2023/2/4
Y1 - 2023/2/4
N2 - Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.
AB - Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9-18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8-20]; two or more prior lines, 13% [95% CI, 7-20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.
KW - Hepatocellular carcinoma
KW - Immunotherapy
KW - Pretreated patient population
KW - Tislelizumab
UR - http://www.scopus.com/inward/record.url?scp=85149114581&partnerID=8YFLogxK
U2 - 10.1159/000527175
DO - 10.1159/000527175
M3 - Article
AN - SCOPUS:85149114581
SN - 2235-1795
VL - 12
SP - 72
EP - 84
JO - Liver Cancer
JF - Liver Cancer
IS - 1
ER -