Concurrent Chemoradiotherapy plus Programmed Death-1 (PD-1) Blockade for Locally Advanced Cervical Cancer: Preliminary Results of a Single-Arm, Open-Label, Phase II Trial

Abstract

This study aims to assess the anti-tumor activity and safety of concurrent chemoradiotherapy plus PD-1 blockade in patients with locally advanced cervical cancer. This is a single-arm, open-label, prospective phase II study. The key inclusion criteria were treatment-naive patients aged 18-75 years with stage II A2-IVA (FIGO 2018) locally advanced cervical cancer. All patients were treated with concurrent chemoradiotherapy including 2 cycle cisplatin (75mg/m2, for three days, every 3 weeks[Q3W]), nedaplatin or carboplatin can be selected for patients who can't tolerate cisplatin. After CCRT, patients achieving complete response (CR), partial responses(PR), stable disease(SD) received adjuvant chemotherapy (docetaxel 75 mg/m2 day 1+ cisplatin DDP 25 mg/m2 day 1-3, Q3W) for 2 cycle. PD-1 blockade Sintilimab and Tislelizumab was administered intravenously at 200 mg every 3 weeks up to 1 year or until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR) assessed by investigators per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Secondary endpoints were the 12, 24-month overall survival (OS) rates, the 12, 24-month disease free survival (DFS) rates and safety. From February 2020 to June 2022, a total of 15 patients was enrolled. Median age was 57 years (range, 36-74 years). Stage IIA1 was documented in 2 patients, stage IIA2 in two patients, stage IIIA in one patient, stage IIIC1 in eight patients, and stage IVA in two patients. And 66.7% (10/15) of patients had Metastatic lymph node. Four patients received adjuvant chemotherapy. The ORR was 100%, with 4 patients achieving CR and 11 PR. The 12 and 24-month OS rates are 93.3% and 84%, the 12 and 24-month DFS rates are 86% and 75.4%, respectively. Treatment-related adverse events (TRAEs) occurred in 86.7% (13/15) of patients. Grade 3 TRAEs are leukocyte (n = 1), thrombocytopenia (n = 1), hepatitis (n = 1), skin reaction (n = 1). No treatment-related deaths occurred. And IFN-γ was significantly elevated after radiotherapy (p = 0.0073). Concurrent chemoradiotherapy plus PD-1 blockade showed promising antitumor activity and manageable toxicities in patients with locally advanced cervical cancer. Long-term outcomes are still pending to further evaluate their therapeutic effects. (ChiCTR2000032856).