Safety and efficacy of toripalimab plus concurrent chemoradiotherapy for locally advanced cervical cancer: a single-arm, phase Ib trial

Although two pivotal phase III trials have evaluated the efficacy of adding immune-checkpoint inhibitors (ICIs) to concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC), discrepancies between the two studies highlight the need for further exploration of ICIs combined with CCRT in this setting.

Totally 30 patients with FIGO 2018 stage IB3-IVA cervical cancer were enrolled in this study. All patients underwent pelvic external beam radiotherapy (50.4 Gy in 28 fractions) followed by brachytherapy (30-36 Gy in 5-6 fractions), concurrent with cisplatin (40 mg/m² weekly) and toripalimab (240 mg every two weeks). The primary endpoint was adverse events, and secondary endpoints included the objective response rate (ORR) and progression-free survival (PFS). This trial is registered at ClinicalTrials.gov (NCT04368273) on April 25, 2020.

Twenty-four patients (80%) experienced grade 3 or higher treatment-related adverse events (TRAEs). The most frequent ≥ grade 3 TRAEs were leukopenia (63%), lymphopenia (37%), and anemia (27%). One patient discontinued treatment due to immune-related hemophagocytic lymphohistiocytosis (HLH). Twenty patients (66.7%) experienced late radiation-related toxicities, including rectal hemorrhage (53.3%), hematuria (10%), and peripheral sensory neuropathy (13.3%). No treatment-related death occurred. All patients showed an ORR of 100% (95% [CI]: 0.85.9-1) as their best response. The 2-year PFS was 90% (95% CI 0.72-0.96). The median PFS was not reached with a 27.3-month follow-up.

Combining toripalimab with CCRT had promising activity in LACC patients but might aggravate radiation-related adverse events and even cause serious immune-related adverse events. Therefore, ICIs therapy with CCRT needs further investigation.