Anlotinib plus chemoradiotherapy in the treatment for FIGO stage IB3 and IIB-IVA cervical cancer: A prospective single-arm, single-center, exploratory phase II trial (299)

Abstract

<b>Objectives:</b> Cervical carcinoma is the fourth leading cause of cancer-related death among women worldwide. Previous randomized clinical trials showed a 30% to 50% decrease in risk of death in locally advanced cervical cancer (LACC) with the addition of concurrent platinum-based chemoradiotherapy when compared with radiotherapy alone. Mechanisms to account for improved efficacy are thought to include direct cytotoxicity, radiosensitization of tumor cells, and control of subclinical metastases. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib synergizes with radiation and cisplatin, as shown in preclinical and clinical studies. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to concurrent chemoradiotherapy in FIGO stage IB3 and IIB-IVA cervical cancer. <b>Methods:</b> Inclusion criteria include treatment-naive histologically confirmed FIGO stage IB3 to IVA cervical cancer with at least one measurable lesion and ECOG performance score 0-2 within the age range of 18 to 75 years. Abundant organ functions are required, with no contraindication to anlotinib or chemoradiation present. Patients will be treated with oral anlotinib (12 mg qd, d1-14; 21 days per cycle; total 3 cycles) and X-ray external-beam radiotherapy (total 45Gy-50Gy in 25-28 fraction), followed by brachytherapy (6Gy/5 fractions or 7Gy/4 fractions) with concurrent cisplatin (40 mg/m2 weekly for 5-6 weeks). The primary endpoint is the progression-free survival (PFS) rate at three years. The secondary endpoints include overall response rate (ORR), disease control rate (DCR), overall survival (OS), and quality of Life (QOL). Safety will be evaluated in all patients who receive study drugs according to the treatment received (safety population) by recording clinical adverse events (AEs) using National Cancer Institute Common. The sample size calculation of 47 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test; considering a 10% reduction, a total of 53 samples are required. This study is currently open, and 23 patients have been enrolled. The estimated primary completion date is December 1, 2024, and the estimated study completion date is October 31, 2025.