Akira Kurosaki

Tegafur-uracil maintenance chemotherapy post-chemoradiotherapy for cervical cancer: Randomized trial

Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but recurrence rates remain high. This multicenter phase-3 randomized trial (GOTIC-002) evaluated the efficacy of low-dose oral tegafur-uracil (UFT) as maintenance chemotherapy following curative CCRT for LACC. Between 2010 and 2018, 351 patients with stage Ib2-IVa cervical cancer were enrolled. After achieving complete or partial remission post-CCRT, patients were randomized 1:1 into observation (arm O) or UFT maintenance therapy (arm UFT). UFT doses were 300-400 mg/day based on body surface area for 2 years, disease progression or adverse effects occurred. The primary endpoint was progression-free survival (PFS), with overall survival (OS) and safety as secondary endpoints. Patient characteristics were similar between the groups (n = 178 in arm O, n = 173 in arm UFT). During a median follow-up of 3 years, median PFS was not reached in either group. 5-year PFS rates were similar between them (arm O: 61.3 %, arm UFT: 62.0 %, hazard ratio: 0.92, P = .634). 5-year OS rates were also comparable (77.6 % vs 76.1 %, hazard ratio: 1.04, P = .869). Compliance with UFT ranged from 87.8 % to 98.8 %. Although adverse events were more frequent in arm UFT (93.5 % vs 73.9 %, odds ratio: 5.05), most were mild or moderate. Despite its tolerability, UFT did not improve PFS or OS. These findings suggest the need to reconsider maintenance therapy strategies after CCRT for potentially shifting away from cytotoxic chemotherapy towards alternative methods to enhance survival outcomes in patients with LACC.

Atezolizumab, bevacizumab, and platinum chemotherapy in cervical cancer: results of Japanese population from BEATcc

This study analyzed the efficacy of add-on atezolizumab to standard first-line bevacizumab-containing therapy in 56 Japanese patients with metastatic and recurrent cervical cancer treated across 8 sites under the Japanese Gynecologic Oncology Group between October 2018 and August 2021 in the BEATcc trial. Patients were randomized to standard arm (standard therapy: cisplatin 50 mg/m² or carboplatin area under the curve of 5, paclitaxel 175 mg/m², and bevacizumab 15 mg/kg) or experimental arm (standard therapy with atezolizumab 1,200 mg). Of 56 patients, 30 were in experimental arm vs. 26, standard arm (age: 53.2±12.9 vs. 54.7±12.2 years). Median progression-free survival was 15.8 months (95% confidence interval [CI]=10.4-26.1) in experimental arm vs. 11.1 months (8.4-16.5) in standard arm (hazard ratio [HR]=0.51; 95% CI=0.26-1.01). Median overall survival was 34.1 months (23.2-38.6) in the experimental arm vs. 31.6 months (16.4-36.5), standard arm (HR=0.53; 95% CI=0.23-1.21). Objective response rate was 86.7% in experimental arm vs. 84.6%, standard arm. Complete response and partial response, respectively, were 23.3% and 63.3% in experimental arm and 26.9% and 57.7% in standard arm. Grade ≥3 adverse events occurred in 80.0%, experimental arm and 88.5%, standard arm. Gastrointestinal/genitourinary fistula incidence was lower in Japanese patients (1 patient receiving atezolizumab), likely due to stricter inclusion criteria. Overall, add-on atezolizumab enhances the efficacy of bevacizumab and chemotherapy in Japanese patients as those in overall BEATcc population and could be considered a new first-line treatment option for metastatic, persistent, or recurrent cervical cancer in Japan. ClinicalTrials.gov Identifier: NCT03556839.