RADT-31. HYPO-FRACTIONATED STEREOTACTIC RE-IRRADIATION (HFSRT) PLUS DURVALUMAB VS HFSRT RE-IRRADIATION ALONE FOR PATIENTS WITH A RECURRENT GLIOBLASTOMA: RESULTS OF THE COMPARATIVE RANDOMIZED PHASE II STERIMGLI TRIAL

Abstract BACKGROUND Hypo-fractionated stereotactic radiotherapy (HFSRT) may enhance anti-PDL1 immunotherapy efficacy in recurrent glioblastoma by promoting immunogenic cell death. After establishing the safety of HFSRT combined with Durvalumab in a phase I trial, we present the results of the randomized phase II STERIMGLI trial (NCT02866747). METHODS Eligible patients with recurrent glioblastoma (WHO 2016 classification) and tumor volume ≤35 mm were randomized 1:2 to receive HFSRT alone (24 Gy in 3 fractions over 5 days, Arm A) or the same HFSRT plus Durvalumab 1500 mg on day 5, then every 4 weeks until progression or 12 months (Arm B). The primary endpoint was overall survival (OS) from randomization. With 100 patients and 77 events, the study had 85% power to detect an HR of 0.57 (one-sided, 10%-level test). RESULTS Between February 2018 and April 2023, 102 patients (median age 61.5 years old, range [26-87]) were randomized (n=34 and 68 in Arm A and B). Baseline characteristics were balanced, except for more prior targeted therapy in Arm B (22.1% vs 2.9%) and more IDH-mutated in Arm A (15.6% vs 6.1%). Treatment was well tolerated, 12.4% of patients experienced grade 3 treatment-related adverse events (no grade 4 or 5). After a median follow-up of 34.1 months, 78 deaths were reported, median OS was 13.3 months in Arm A vs, 16.1 months in Arm B (Hazard Ratio (HR)=0.77, 80%CI = [0.56;1.06], one-sided p=0.146). In multivariate analysis, adjusted HR for prognostic factors was 0.41 (80%CI = [0.28;0.60]). Among patients with IDH-wildtype glioblastoma (WHO 2021), median OS was 10.9 vs, 16.1 months (HR=0.54, 80%CI=[0.39;0.76], one-sided p=0.010). The median intracranial progression-free interval assessed by investigators with RANO criteria was 2.3 vs, 3.5 months (HR=0.91, 80%CI=[0.68;1.23], one-sided p=0.349). CONCLUSION Re-irradiation with HFSRT (24 Gy/3 fractions) combined with Durvalumab is safe and improves overall survival in patients with recurrent glioblastoma.