ESTRO 2025 - Abstract Book

S800

Clinical - Gynaecology

ESTRO 2025

Medicine, Tata Memorial Hospital,Tata Memorial Centre, Mumbai, India. 6 Department of Medicine, ACTREC,Tata Memorial Centre, Navi Mumbai, India. 7 Clinical Pharmacology, ACTREC,Tata Memorial Centre, Navi Mumbai, India. 8 Medical Oncology, ACTREC,Tata Memorial Centre, Navi Mumbai, India. 9 Medical Oncology, Tata Memorial Hospital,Tata Memorial Centre, Mumbai, India. 10 Bioimaging and Nuclear Medicine, Tata Memorial Hospital,Tata Memorial Centre, Mumbai, India. 11 Radiodiagnosis, Tata Memorial Hospital,Tata Memorial Centre, Mumbai, India Purpose/Objective: Advances in image-guided adaptive brachytherapy (IGBT) and chemoradiation (CRT) have improved pelvic control; however, disease-free survival (DFS) continues to be modest in Stage III cervical cancer. Upregulation of Phosphoinositide-3-kinase-protein kinase B (p13K-AKT) pathway leads to therapeutic resistance, and addition of protease inhibitors (Nelfinavir) to CRT and IGBT could improve DFS. Material/Methods: NCT03256916 was designed as an open label, parallel group phase III trial. Patients with stage III cervical cancer (FIGO 2018) were randomized to either CRT-IGBT (standard arm), or in combination with Nelfinavir (test arm). CRT included Image guided-intensity modulated radiotherapy (IG-IMRT) (45Gy/25#) and nodal boost up to 55 Gy/25/5 weeks for involved nodes and concurrent weekly cisplatin (40 mg/m 2 ). All patients underwent MRI-based brachytherapy. No prophylactic lower paraaortic irradiation was used. Patients in the test arm received Nelfinavir 1250 mg two times a day, starting 7-10 days before CRT and continued through CRT. The primary endpoint was 3-year DFS. The overall sample size was 348, with early interim analysis for futility at 32 events(80% power to detect a hazard ratio (HR) of 0.66. Results: Futility analysis was performed at 32 events. The median follow-up was 30 months. The FIGO 2018 stage was IIIA-B in 43.5%, IIIC1 in 48.9% and Stage III C2 in 7.6%. The median high risk clinical target volume at brachytherapy was 34.3 cc (IQR 26-48 cc) with a median D90 of 88.2 Gy (IQR 83-92.2Gy). A median of 5 cisplatin cycles were administered and duration of Nelfinavir was 43 days (IQR 42-47 days). The median overall treatment time was 50 days (IQR 47-55). Local, pelvic, paraaortic and distant recurrences were observed in 9.8%, 10.9%, 6.5% and 16.3% patients, respectively, with overall 32 events (18 in test and 14 in standard arm). This corresponded to 3-year DFS of 52.2% in the test arm and 68% in the standard arm (HR 1.30, 95% CI 0.64-2.6, p=0.45). The z-value was 0.74 which did not cross futility bounds (-4.75, +4.75). Additionally, the conditional power indicated futility index of 0.44 with two sided type-1 error of 0.05. Though the futility bounds were not exceeded, no statistically significant improvement was observed with Nelfinavir with numerically superior outcomes in the standard arm.

Fig 1: 3 year DFS at Futility Analysis.