300 - Comparison of Docetaxel and Cisplatin Concurrent and Short-Course Adjuvant Chemotherapy with Cisplatin Concurrent Chemotherapy in Radiotherapy for Locally Advanced Cervical Cancer: A Phase III Multice

Y. Zhang, H. Yang, Y. Yin, W. Li, J. Li, W. Zhou, L. Wei, M. Shi, and L. Zhao; Department of Radiation Oncology, First Affiliated Hospital of Air Force Medical University, Xian, China

Purpose/Objective(s): To assess the efficacy and safety of concurrent and adjuvant docetaxel plus cisplatin triweekly chemotherapy compared with current standard of cisplatin weekly in locally advanced cervical cancer (LACC) radiation. Materials/

Methods: In this multicenter, randomized, phase 3 trial, eligible participants were aged 18 year or older, with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the LACC (FIGO 2008 stage IB2 to IVA), ECOG performance status 0–2, no history of tumor-related treatment, and adequate bone marrow and organ function. Participants were randomly assigned (1:1) to two groups on the basis of receiving pelvic external beam radiation therapy (EBRT) and brachytherapy: concurrent cisplatin (DDP) 40 mg/m² intravenously weekly with EBRT (CCRT) , or CCRT+ACT group: concurrent cisplatin 60 mg/m² and docetaxel 60 mg/m² triweekly with EBRT, and followed by two triweekly cycles of cisplatin 75 mg/m² and docetaxel 75 mg/m². The primary endpoint was progress-free survival (PFS) at 3 years, analyzed in the intention-to-treat population. Safety was assessed in all patients who started chemoradiotherapy.
Results: Between November 22, 2016 and December 31, 2019, 625 patients were enrolled and randomly assigned to the CCRT group (n=303) or CCRT+ACT group (n=322), of whom 573 were eligible for intention-to-treat analysis (297 in the CCRT group and 276 in the CCRT+ACT group. The median age of all patients was 53 years (IQR 48 to 58), squamous cell carcinoma accounted for 89.0%, and the median maximum diameter of primary cervical tumor was 4.6cm (IQR 3.8 to 5.6). 155 cases (27.1%) were FIGO I-II stage and 383 cases (66.8%) were FIGO III-IVA stage. During EBRT, 228/234 patients (97.4%) received 2 cycle of DP concurrent chemotherapy, and 184/228 (80.7%) patients completed at least one cycle of adjuvant chemotherapy. Up to the follow-up time (June 22, 2023, median follow-up time 45 months), 3-year PFS was 78.5% in CCRT group versus 78.5% in CCRT+ACT group (P=0.538). OS at 3 years was 84.1% and 84.1% in two groups respectively (P=0.823). There were also no significant differences in 3-year DMFS and LRFS between the two groups. At 5 years, PFS and OS were 72.5% and 79.9% in CCRT group, 76.6% and 77.4% in CCRT+ACT group, respectively. In subgroup analysis using different FIGO stages, pelvic lymph node metastasis, metastasis lymph node number, and tumor maximum diameter, there was still no significant difference in OS and PFS between the two groups. Compared with standard cisplatin, incidence of Grade 3 and 4 acute thrombopenia increased during DP concurrent chemoradiation (thrombopenia, 6.0% vs 2.4%, P =0.048).
Conclusion: Docetaxel plus cisplatin concurrent chemotherapy combined with adjuvant chemotherapy is clinically well tolerated. However, compared with standard cisplatin monotherapy, the use of the two-drug combination did not significantly improve LACC survival. This trial is registered with ClinicalTrials.gov, NCT02703961.