Polymeric micellar paclitaxel plus cisplatin combined with tislelizumab as the first-line treatment of advanced unresectable esophageal squamous cell carcinoma: A phase II study.

e16022 Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced and metastatic esophageal squamous cell carcinoma (ESCC). However, the prophylactic use of hormones, a routine preconditioning regimen of paclitaxel, may weaken the immune response. Polymeric micellar paclitaxel is a new formulation of paclitaxel without polyoxyethylene castor oil solvent, which do not need for pretreatment with anti-allergy drugs before administration. We aimed to evaluate the efficacy and safety of polymeric micellar paclitaxel (pm-Pac) plus cisplatin combined with tislelizumab for unresectable advanced ESCC. Methods: This is a single-center, single-arm, prospective phase II clinical trial. Stage IV ESCC patients diagnosed histologically or cytologically without systemic treatment are eligible for this study. Polymeric micellar paclitaxel plus cisplatin combined with tislelizumab was treated for 2 cycles. After imaging evaluation, if there was no disease progression, an additional two cycles of treatment were completed, followed by maintenance treatment with tislelizumab for one year. At day 1 of each therapy cycle, patients were given pm-Pac 230 mg/m2 followed by cisplatin 70 mg/m2 combined with tislelizumab 200 mg via intravenous infusion, every three weeks. This trial planned to include 30 patients. The primary endpoint was objective response rate (ORR) determined by the independent review committee. And the secondary endpoints included overall survival, progression-free survival evaluated based on the Response Evaluation Criteria in Solid Tumors (version 1.1), as well as the incidence and severity of adverse events. Results: From September 2022 to January 2024, 31 patients were included in the trial. Median age was 65 years, 29 (93.5%) patients were male. Median follow-up was 13.1 months, 2 patient achieved complete response (CR), 19 of them showed partial response (PR), 8 stable disease (SD), illustrating an ORR of 67.7% and a DCR of 93.5%. Median PFS was 7.3 months. The most common AEs were neutropenia (90.3%), nausea(83.8%) and thrombocytopenia (25.8%). No grade 3 or higher immune-related AE was observed, and there were no treatment-related deaths. Conclusions: The pm-Pac plus cisplatin combined with tislelizumab as first-line treatment of unresectable advanced ESCC showed effective without new safety signal. This combination therapy may have great efficacy, but multi-center randomized trials with larger sample size are warranted in further.