The First Affiliated Hospital of Air Force Medical University Xi’an, Shaan’xi
H. Yang1,2, M. Dong3, J. Zhang4, Y. Zhang1, W. Li1, Y. Zhu5, Y. Wang6, L. C. Wei1, and L. N. Zhao1; 1Department of Radiation Oncology, First Affiliated Hospital of Air Force Medical University, Xian, China, 2Department of Radiation Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi an, Shaanxi, China, 3Department of Medical Education, the First Affiliated Hospital of Air Force Medical University, Xi an, Shaanxi, China, 4Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan., chengdu, China, 5Department of Radiotherapy, Baoji Central Hospital, baoji, Shaanxi, China, 6Department of Radiation Oncology, the Second Affiliated Hospital of Xi an Jiaotong University, Xian, China
Purpose/Objective(s): Platinum-based concurrent chemoradiotherapy is the standard of care for patients with high-risk locally advanced cervical carcinoma,the value of adding induction chemotherapy to concurrent chemoradiotherapy is unclear. We aimed to compare induction chemotherapy plus concurrent chemoradiotherapy(IC+CCRT) with concurrent chemoradiotherapy(CCRT) alone has shown promising efficacy in phase 2 trials. Materials/
Methods: We did an open-label, phase 2, multicenter, randomized controlled trial at four institutions in China. Patients with previously untreated, FIGO 2018 stage IB3-IIIB (tumor diameter = 5cm disease) or stage IIIC cervical carcinoma, aged 27–70 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive IC+CCRT or CCRT (5 cycles of 40 mg/m² cisplatin every week, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was two cycles of intravenous docetaxel (75 mg/m² on day 1), intravenous cisplatin (75 mg/m² on day 1), and intravenous Bevacizumab (7.5 mg/kg on day 1) every 3 weeks before CCRT. The primary endpoint was failure-free survival calculated from randomization to locoregional failure, distant failure, or death from any cause; required sample size was 238 patients (119 per group). Secondary end points included overall survival, treatment adherence, and safety. Results: Between April 2, 2019, and Sep 22, 2022, 119 patients were assigned to IC+CCRT and 119 to CCRT. Median age 48(range 27-70) years. Stage distribution was IB3-IIIB (tumor diameter = 5cm disease):24.4%; IIIC1:48.7%; IIIC2:26.9%; Median interval from IC to CCRT was 20 days. 98.3% (IC+CCRT) vs. 99.2% (CCRT alone) completed external beam and brachytherapy respectively. The median overall treatment time for CCRT was 52 days in both arms. Grade =3 adverse events were 52.9% (IC+CCRT) vs. 47.9% (CCRT alone). After a median follow-up of 36 months. 3-year progression-free survival(PFS)rate was 84.9% with IC+CCRT and with 75.1% CCRT alone (HR 0.53, 95% CI 0.28-0.97; p=0.04). The corresponding 3-year OS rate were 88.6% and 78.4% (HR 0.53, 95% CI 0.28-0.98; p=0.043). Conclusion: Induction chemotherapy followed by concurrent chemoradiotherapy significantly improved PFS and OS in high-risk locally advanced cervical carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities.
