SURG-01. OPTIMALTTF-1: FINAL RESULTS OF A PHASE 1 STUDY: FIRST GLIOBLASTOMA RECURRENCE EXAMINING TARGETED SKULL REMODELING SURGERY TO ENHANCE TUMOR TREATING FIELDS STRENGTH

Abstract

Abstract BACKGROUND OptimalTTF-1(open-label phase-1) combines Tumor Treating Fields(TTFields) treatment with targeted skull-remodeling surgery(SR-surgery) aiming to enhance the electric field strength in the tumor(NCT02893137). SR-surgery aims to reduce the electrical impedance of the skull. Pre-clinical modeling indicates that SR-surgery increases the electric field strength. The final analysis examined toxicity and efficacy of TTFields combined with SR-surgery and best-choice-chemotherapy in first glioblastoma recurrence(rGBM). METHODS 18 patients were screened and 15 (4F/11M) enrolled between Dec2016 and Mar2019. The primary endpoint was frequency of serious adverse events (CTCAEv4.0) and secondary endpoints were overall survival (OS) and progression-free survival (PFS). Eligible patients were ≥18-years, had focal supratentorial rGBM, KPS≥70, and a minimum calculated increase in TTFields strength of ≥25% after SR-surgery. At the time-of-analysis patients were censored for time-to-event endpoints. RESULTS Baseline data(median (range)) demonstrated a patient age of 57(39;67), skull defect area=10.6 cm2(7;37), increase in the TTFields strength by 43%(25;59). All tumors were IDH-wt and 4 had MGMT-promoter methylation. In total, 4 patients were excluded from the study prior to TTFields initiation (consent withdrawal, radionecrosis/non-recurrence, postoperative infection and neurodeficit), 11 patients (2F/9M) underwent treatment. Treatment compliance was 90%(48;98), mean treatment duration and follow-up was 6.8 months(2.3;20.4) and 10 months respectively. Grade 1–2 AEs included, headache 60% CI95%=[32;84], fatigue 53%, CI95%=[27;79], skin rash 47%, CI95%=[21;73], and nausea 40%, CI95%=[16;68]. No grade 3 SAEs were related to the intervention (6 seizures, 1 headache, 1 fatigue, 1 TIA, 1 post-op infection, 1 diarrhea and 1 DVT). Efficacy outcomes were PFS6=64%, CI95%=[35;85], PFS=8.8 months, CI95%=[6.2;13.2], OS=15.0 months, CI95%=[9.6;16.2], and OS12=64%, CI95%=[35;85]. CONCLUSION Targeted SR-surgery combined with TTFields is safe and does not induce additional toxicity. Furthermore, it potentially increases overall survival in rGBM. A phase 2 clinical trial is currently being planned.