Toripalimab plus chemotherapy and radiotherapy for treatment-naive, advanced esophageal squamous cell carcinoma: A single-arm phase II trial

Abstract Background The effectiveness of chemo-immunotherapy for advanced esophageal squamous cell carcinoma (ESCC) remains limited. Therefore, we evaluated the safety and efficacy of radiotherapy plus chemo-immunotherapy as a first-line therapy for advanced ESCC. Methods In this single-arm clinical trial, individuals aged 18–75 years with previously untreated stage IV ESCC received chemotherapy comprising four cycles of 135–175 mg/m 2 paclitaxel with carboplatin every three weeks. Toripalimab (240 mg) was intravenously infused every three weeks for 12 months or until disease progression or intolerable toxicity. Radiotherapy commenced in the third cycle, encompassing radiation (50–50.4 Gy in 25–28 fractions) to primary lesions and metastases (30–40 Gy in 3–5 fractions). The primary outcome was progression-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), duration of remission (DoR), one- and two-year overall survival rates, and adverse events. Results In this study, 33 participants (29 men; median age 59 years) were enrolled. Ultimately, 26 patients (78.8%) completed the entire radio-chemotherapy course, achieving an ORR, DCR, and DoR of 57.7% (95% CI: 37.3–78.0), 73.1% (95% CI: 54.8–91.3), and 11.5 months (IQR, 6.4–15.0 months), respectively. Within a median follow-up of 22.2 months, the median PFS was 12.8 months. Lymphopenia was the most frequent grade ≥ 3 adverse event (82%), and esophageal fistula occurred in three patients (9.1%). No treatment-related deaths occurred. Conclusion Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated substantial antitumor activity and manageable safety, warranting further randomized controlled trials. Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=126830 , identifier ChiCTR2100046715.