QOL-26. A RANDOMIZED, DOUBLE-BLIND PHASE 3 STUDY OF VORASIDENIB VS PLACEBO IN PATIENTS WITH MUTANT <i>IDH1/2</i>DIFFUSE GLIOMA (INDIGO): ANALYSIS OF HEALTH-RELATED QUALITY OF LIFE, NEUROCOGNITION AND SEIZURES
Katherine B. Peters, Ingo K. Mellinghoff, Martin J. van den Bent, Deborah T. Blumenthal, Mehdi Touat, Jennifer Clarke, Joe Mendez, Shlomit Yust‐Katz, Warren Mason, François Ducray, Yoshie Umemura, Burt Nabors, Matthias Holdhoff, Andreas F. Hottinger, Yoshiki Arakawa, Juan Manuel Sepúlveda-Sánchez, Wolfgang Wick, Riccardo Soffietti, James Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Andrew Bottomley, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, Timothy F. Cloughesy
Abstract
Abstract INTRODUCTION The Phase 3 INDIGO study (NCT04164901) is a randomized, double-blind evaluation of vorasidenib, an oral, brain-penetrant inhibitor of mutant isocitrate dehydrogenase (mIDH) 1/2 enzymes, compared with placebo, in patients with grade 2 mIDH1/2 diffuse gliomas, whose only prior treatment was surgery. The primary endpoint, radiographic progression-free survival by blinded independent review committee, and the key secondary endpoint, time-to-next-intervention, were significantly improved with vorasidenib versus placebo. As these patients are young, with several years’ life expectancy, impact of treatments on health-related quality of life (HRQoL), cognition and symptomatic burden is of interest. METHODS HRQoL, assessed by Functional Assessment of Cancer Therapy-Brain (FACTBr) questionnaire, was a secondary endpoint. FACT-Br was collected at baseline, Cycles 2 and 3, then every 3 months. Scores were interpreted using an estimate of clinically meaningful deterioration change from baseline for each arm. Exploratory endpoints included neurocognitive function, assessed by a validated battery of cognitive performance instruments, and seizure frequency and severity, assessed using a subject diary. RESULTS 331 patients were randomized to vorasidenib (n = 168) or placebo (n = 163) (median age, 40.0 years; Karnofsky performance scale = 100, 53.5%; ongoing medical history of seizures, 54.1%). Median follow-up was 14.2 months. No clinically meaningful deterioration from baseline FACT-Br total score and subscales were observed at any timepoint through the median treatment duration (Cycle 13) in either arm. At baseline, active seizures (≥ 1 seizure in the previous 30 days) were reported in 20/168 (11.9%) vorasidenib patients and 20/163 (12.3%) placebo patients. On-treatment seizure frequencies and cognition outcomes will be presented by arm. CONCLUSION INDIGO is the first randomized Phase 3 study of targeted therapy in grade 2 mIDH1/2 diffuse glioma. HRQoL, as measured by FACT-Br, was maintained during treatment with vorasidenib. These data support the clinical benefit of vorasidenib in this patient population for whom chemotherapy and radiotherapy are being delayed.