Phase II Study of Toripalimab in Combination with Induction Chemotherapy and Subsequent Chemo- Radiation in Patients with Advanced/Metastatic Esophageal Carcinoma (TR-EAT Trial)

Abstract

<h3>Purpose/Objective(s)</h3> Immune checkpoint inhibitor therapy combined with chemotherapy is safe and effective in treating advanced esophageal carcinoma; however, some patients still experience tumor progression and/or metastasis. Whether the addition of radiotherapy to immunotherapy combined with chemotherapy improves the prognosis of patients with advanced/metastatic esophageal carcinoma needs to be investigated. <h3>Materials/Methods</h3> This is an open-label, single-arm, and single-center phase II trial. Patients with unresectable stage IV esophageal squamous cell carcinoma (ESCC) who had not received prior systemic therapy were enrolled. The patients were treated with two cycles of toripalimab (240 mg d1, Q3w) combined with induction chemotherapy (paclitaxel 135-175 mg/m2, d1+carboplatin AUC=4-6, d1, Q3W), sequentially combined with concurrent chemoradiotherapy (30-50 Gy in 15-25 fractions, paclitaxel 135-175 mg/m2, d1+carboplatin AUC=4-6 d1, Q3W), followed by maintenance treatment with toripalimab (240 mg d1, Q3W) for 1 year. The primary objective of this trial is to evaluate the progression-free survival (PFS) of this combination therapy; and the secondary objective is related to the assessment of objective response rate (ORR), the disease control rate (DCR), the duration of remission (DOR), the 1-and 2-year overall survival (OS) rates, the safety and tolerability of patients to treatment, and the identification of the changes in the health-related quality of life (HRQoL) of patients. <h3>Results</h3> Up to date, a total of 23 patients were screened, and 22 were enrolled. The median age of the patients was 58 years (range, 43-70 years), and 19 patients were males. Four patients completed two cycles of chemotherapy combined with immunotherapy, two patients were in the concurrent chemoradiotherapy phase, and 10 patients were in the immune maintenance phase. The median follow-up period was 4.3 months (1.3-8.2 months). After two cycles of chemotherapy combined with immunotherapy, treatment results of 18 patients were evaluated. The results showed complete response (CR) in 0 patients, partial response (PR) in 6, stable disease (SD) in 9 and progressive disease (PD) in 3. ORR was 33.3% and DCR was 83.3%. After concurrent chemoradiotherapy, the treatment results of 11 patients were evaluated. The results showed CR in 1 patient, PR in 8, SD in 2 and PD in 0. ORR was 81.8% and DCR was 100%. Most patients experienced only grade 1-2 adverse effects and laboratory abnormalities, and no grade 3 or worse adverse effects or laboratory abnormalities occurred. <h3>Conclusion</h3> The interim analysis showed that the sequential CRT therapy is proved to be effective in the initial treatment of advanced esophageal squamous cell carcinoma (ESCC) after the treatment with toripalimab combined with chemotherapy. The initial results are encouraging and the final results are to be expected.