[A prospective phase Ⅱ clinical trial of toripalimab combined with platinum-based concurrent chemoradiotherapy and consolidation chemotherapy in patients with locally advanced cervical cancer].

Objective: To explore the efficacy and safety of toripalimab combined with platinum-based chemoradiotherapy in the treatment of locally advanced cervical cancer. Methods: A total of 82 patients diagnosed as locally advanced cervical cancer who received toripalimab combined with platinum-based concurrent chemoradiotherapy at Tianjin Medical University Cancer Institute and Hospital from May 24^th 2019 to August 31^st 2022 were enrolled prospectively. After undergoing concurrent chemoradiotherapy, the patient received six cycles of treatment with toripalimab in combination with paclitaxel and platinum-based agents. The primary endpoint of the study was the objective response rate (ORR), and the secondary endpoints included disease control rate (DCR), safety, progression-free survival, and overall survival. Kaplan-Meier curves were used to depict the cumulative incidence of progression-free survival (PFS) and overall survival (OS) for patients with different expression levels of programmed death-ligand 1 (PD-L1) and genetic mutation burdens, and log-rank tests were used to compare the difference between groups. Results: The median age of the patients was 53.6 (45.5,58.7) years, and 76 patients (92.7%) had squamous cell carcinoma. The overall ORR and DCR for the 82 patients were both 87.8% (72 patients, 95%CI: 78.7%-94.0%). Among the 82 patients, 64 (78.0%) achieved complete remission, 8 (9.8%) had partial remission, 8 (9.8%) had disease progression, and 2 (2.4%) were not evaluable. During the treatment, 37 patients (45.1%) experienced treatment-related adverse events, of which 17 patients (20.7%) had grade 3 or higher adverse reactions. The most common grade 3 or higher treatment-related adverse reaction was radiation enteritis (n=5, 6.1%). The median follow-up time was 20.6 (14.0, 27.9) months. The median progression-free survival (mPFS) and median overall survival (mOS) were not reached. The 2-year PFS rate was higher in patients with PD-L1 combined positive score (CPS)≥10 compared to those with CPS<10 (92.4% vs 81.2%, χ²=0.68, P=0.409), and higher in patients with low tumor mutation burden (TMB-L) compared to those with high tumor mutation burden (TMB-H) (95.2% vs 83.3%, χ²=1.91, P=0.167). Conclusion: Patients with locally advanced cervical cancer can achieve favorable objective response rates when treated with toripalimab in combination with platinum-based concurrent chemoradiotherapy and consolidative chemotherapy.