Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial

• Published in: Nature communications Vol. 15; no. 1; pp. 7116 - 12
• Main Authors: Wu, Lei, Li, Baisen, Wan, Gang, Wang, Yi, Zhu, Jie, Liang, Long, Leng, Xuefeng, He, Wenwu, Peng, Lin, Han, Yongtao, He, Shuya, Wang, Dongsheng, Zhou, Yehan, Yi, Liang, Zhang, Wencheng, Pang, Qingsong, Zhang, Wei, Li, Tao, Lang, Jinyi, Liu, Yang, Cao, Bangrong, Wang, Qifeng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/21; 13/31; 13/51; 631/67/1059/485; 631/67/1857; 692/4028/67/1059/2325; Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Biomarkers; Carboplatin; Carboplatin - administration & dosage; Carboplatin - therapeutic use; CD11c antigen; CD8 antigen; Chemoradiotherapy - methods; Chemotherapy; Clinical trials; Confidence intervals; Dendritic cells; Disease control; Esophageal cancer; Esophageal carcinoma; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophageal Neoplasms - radiotherapy; Esophageal Neoplasms - therapy; Esophageal Squamous Cell Carcinoma - drug therapy; Esophageal Squamous Cell Carcinoma - mortality; Esophageal Squamous Cell Carcinoma - pathology; Esophageal Squamous Cell Carcinoma - radiotherapy; Esophageal Squamous Cell Carcinoma - therapy; Esophagus; Female; Humanities and Social Sciences; Humans; Immunotherapy; Lymphocytes; Lymphocytes T; Lymphopenia; Macrophages; Male; Medical prognosis; Metastases; Middle Aged; multidisciplinary; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; PD-1 protein; Progression-Free Survival; Radiation therapy; Safety management; Science; Science (multidisciplinary); Squamous cell carcinoma; Survival; Toxic diseases; Toxicity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-51105-2

This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8–not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4–15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7–63.5) and 69.7% (95% CI: 55.7–87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials. Chemo-immunotherapy regimens are now recommended as first-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC), however survival outcomes remain unsatisfactory. Here the authors report the results of a phase 2 trial of toripalimab (anti-PD1) plus chemotherapy and radiotherapy in patients with treatment-naïve advanced ESCC.