The efficacy and safety of tislelizumab plus bevacizumab and chemotherapy as first line therapy in patients with persistent, recurrent, or metastatic cervical cancer: A multicenter, phase II study.
Authors: Zhu Jianqing , Pan Mei , Yu Hao , Chao Hongtu , Chen Youguo , Zhao Hongqin , Niu Shuhuai , Gao Yuhua , Wen Qiang 
Published: June 2023

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Background: Patients (pts) with persistent, recurrent, or metastatic cervical cancer are at high risk of progression after first line standard treatment with platinum-doublet chemotherapy ± bevacizumab. The addition of programmed death-1 (PD-1) inhibitor to this standard treatment has shown improved survival profiles in pts with PD-L1 positive. This study aims to investigate the efficacy and safety of PD-1 inhibitor (tislelizumab) plus bevacizumab and platinum-doublet chemotherapy as the first line therapy in pts regardless of the PD-L1 expression status. Methods: Pts with persistent, recurrent, or metastatic cervical cancer were enrolled and received tislelizumab 200 mg + bevacizumab 7.5 mg/kg + cisplatin 50 mg/m2 or carboplatin AUC5 + paclitaxel 175 mg/m2 IV D1 Q3W. This study comprised two parts: safety run-in (Part 1) and cohort expansion (Part 2). In Part 1, a total of 6 pts were enrolled and underwent safety assessment during the first treatment cycle (21 days). If no more than 2 of 6 pts were observed with dose-limiting toxicity (DLT), pts will be allowed to continue treatment and additional 43 pts will be enrolled (Part 2). The primary endpoint was progression-free survival. A one-sample log-rank test with a total sample size of 49 pts with one sided alpha of 5%, achieved 85% power to detect a difference in PFS between the investigated treatment and historical control. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and safety and tolerability. Results: We report the preliminary results of this study. No DLT was observed among the first 6 pts in Part 1 stage and the study proceeded to the Part 2. Until Oct 28, 2022, a total of 24 pts were enrolled with the median age of 56.0 years. 6 (25.0%) pts were diagnosed with stage IV disease at the study entry and 21 (87.5%) were with squamous cell carcinoma. At the data cutoff time of Nov 30, 2022, among the 19 efficacy evaluable pts, the unconfirmed ORR was 73.7% (14/19, 95% CI: 48.8%-90.8%), and the DCR was 100% (19/19, 95% CI: 82.3%-100.0%). With the median follow up time of 3.8 months, DOR was not reached. The incidence of treatment related adverse events (TRAEs) of any grade was 79.2% (19/24), and grade ≥3 TRAEs occurred in 45.8% (11/24) pts. Most common TRAEs (≥20%) of any grade were anemia (58.3%, 14/24), decreased platelet count (37.5%, 9/24), alopecia (29.2%, 7/24), decreased white blood cell count (25.0%, 6/24), and weight decreased (20.8%, 5/24). Immune related adverse events were all grade 1-2 (16.7%, 4/24). Severe adverse events were reported in 4 (16.7%) pts. Conclusions: Tislelizumab plus bevacizumab and chemotherapy showed preliminary promising efficacy and was well-tolerated as the first line therapy in pts with persistent, recurrent, or metastatic cervical cancer. Clinical trial information: NCT05247619 .