3093 - Toripalimab plus Chemotherapy and Radiotherapy for Treatment-Naive, Advanced Esophageal Squamous Cell Carcinoma: A Single-Arm Phase II Trial

Q. Wang¹, L. Wu¹, L. Liang², Y. Wang¹, L. Peng³, Y. Han³, T. Li², and J. Lang⁴; ¹Department of Radiation Oncology, Sichuan Cancer Hospital and Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Radiation Oncology Key Laboratory of Sichuan Province, Chengdu, China, ²Department of Radiation Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China, ³Department of Thoracic Surgery, Sichuan Cancer Hospital& Institution, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, ⁴Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center; Cancer Hospital affiliate to University of Electronic Science and Technology of China, Chengdu, China

Purpose/Objective(s): The effectiveness of chemo-immunotherapy for advanced esophageal squamous cell carcinoma (ESCC) remains limited. Therefore, we evaluated the safety and efficacy of radiotherapy plus chemoimmunotherapy as a first-line therapy for advanced ESCC. Materials/

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/m2 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. Trial Registration: ChiCTR2100046715.
Results: From 30 June 2021 to 30 September 2022, we assessed 56 patients for eligibility; among whom, 33 (median age: 59 years, range: 43–74; 29 men) were enrolled. The most common sites for oligometastasis were distant lymph nodes (63.6%), followed by the lungs (15.2%), and bones (9.1%). We observed that 27 (81.8%) patients had a total of 32 oligometastatic lesions, of which 12 were in distant organs and 15 in non-regional lymph nodes, whereas 6 patients (18.2%) had only regional lymph node metastases (cTanyN3M0). Treatment was permanently stopped prior to the commencement of radiotherapy in five patients for the following reasons: informed consent withdrawal (n = 1), supraventricular arrhythmia (n = 1), esophageal fistulae (n = 2), and disease progression (liver metastasis; n = 1). Among the 28 patients who started radiotherapy, one withdrew consent after completing three sessions of radiotherapy, and another refused radiotherapy for liver metastasis after completing radiotherapy for the primary lesion. 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 1-year PFS and OS rate was 50.0% (95% CI:34–73.4%) and 76.9% (95% CI: 62.3–94.9%), respectively. The median PFS was 12.8 months (95% CI: 8.0 months–not estimable) and the median OS was not attained. 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.