Second-line tislelizumab versus chemotherapy in Japanese patients with advanced or metastatic esophageal squamous cell carcinoma: subgroup analysis from RATIONALE-302

Hiroki Hara; Taroh Satoh; Takashi Kojima; Takahiro Tsushima; Yu Sunakawa; Morihito Okada; Ningning Ding; Hongqian Wu; Liyun Li; Tian Yu; Gisoo Barnes; Ken Kato

doi:10.1007/s10388-023-01040-w

Second-line tislelizumab versus chemotherapy in Japanese patients with advanced or metastatic esophageal squamous cell carcinoma: subgroup analysis from RATIONALE-302

Esophagus. 2024 Apr;21(2):102-110. doi: 10.1007/s10388-023-01040-w. Epub 2024 Jan 19.

Authors

Hiroki Hara¹, Taroh Satoh², Takashi Kojima³, Takahiro Tsushima⁴, Yu Sunakawa⁵, Morihito Okada⁶, Ningning Ding⁷, Hongqian Wu⁸, Liyun Li⁷, Tian Yu⁹, Gisoo Barnes⁸, Ken Kato¹⁰

Affiliations

¹ Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan.
² Osaka University Hospital, Suita, Japan.
³ National Cancer Center Hospital East, Chiba, Japan.
⁴ Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
⁵ Department of Clinical Oncology, St. Marianna University School of Medicine, Kanagawa, Japan.
⁶ Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
⁷ BeiGene, Ltd, Zhongguancun Life Science Park, Beijing, China.
⁸ BeiGene, Ltd, Ridgefield Park, NJ, USA.
⁹ Clinical Pharmacology, BeiGene USA, Inc., San Mateo, CA, USA.
¹⁰ Department of Head and Neck Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. kenkato@ncc.go.jp.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis, with limited second-line systemic therapy options, and represents an increasing disease burden in Japan. In the phase 3 RATIONALE-302 study, the anti-programmed cell death protein 1 antibody, tislelizumab, significantly improved overall survival (OS) versus chemotherapy as second-line treatment for advanced/metastatic ESCC. Here, we report the Japanese patient subgroup results.

Methods: Patients with advanced/metastatic ESCC, with disease progression during/after first-line systemic therapy were randomized 1:1 to open-label tislelizumab 200 mg every 3 weeks or investigator's choice of chemotherapy (paclitaxel/docetaxel). Efficacy and safety were assessed in all randomized Japanese patients.

Results: The Japanese subgroup comprised 50 patients (n = 25 per arm). Tislelizumab improved OS versus chemotherapy (median: 9.8 vs. 7.6 months; HR 0.59; 95% CI 0.31, 1.12). Among patients with programmed death-ligand 1 score ≥ 10%, median OS was 12.5 months with tislelizumab (n = 10) versus 2.9 months with chemotherapy (n = 6) (HR 0.31; 95% CI 0.09, 1.03). Tislelizumab improved progression-free survival versus chemotherapy (median: 3.6 vs. 1.7 months, respectively; HR 0.50; 95% CI 0.27, 0.95). Objective response rate was greater with tislelizumab (32.0%) versus chemotherapy (20.0%), and responses were more durable (median duration of response: 8.8 vs. 2.6 months, respectively). Fewer patients experienced ≥ grade 3 treatment-related adverse events with tislelizumab (24.0%) versus chemotherapy (47.8%). Tislelizumab demonstrated an improvement in health-related quality of life versus chemotherapy.

Conclusions: As second-line therapy for advanced/metastatic ESCC, tislelizumab improved OS versus chemotherapy, with a favorable safety profile, in the Japanese patient subgroup, consistent with the overall population.

Clinical trial registry: ClinicalTrials.gov: NCT03430843.

Keywords: Esophageal squamous cell carcinoma; Japan; Programmed cell death protein 1 inhibitor; Tislelizumab.

MeSH terms

Antibodies, Monoclonal, Humanized*
Clinical Trials, Phase III as Topic
Esophageal Neoplasms* / pathology
Esophageal Squamous Cell Carcinoma* / drug therapy
Humans
Japan / epidemiology
Quality of Life
Randomized Controlled Trials as Topic

Substances

Antibodies, Monoclonal, Humanized
tislelizumab

Associated data

ClinicalTrials.gov/NCT03430843