A Randomized, Double-blind, Phase 3 Study of Vorasidenib Versus Placebo in Patients with Mutant IDH1/2 Diffuse Glioma (INDIGO): Analysis of Health-related Quality of Life, Neurocognition and Seizures
Katherine Peters1, Ingo Mellinghoff2, Martin Van Den Bent3, Deborah Blumenthal4, Mehdi Touat5, Jennifer Clarke6, Joe Mendez7, Shlomit Yust-Katz8, Warren Mason9, Francois Ducray10, Yoshie Umemura11, Burt Nabors12, Matthias Holdhoff13, Andreas Hottinger14, Yoshiki Arakawa15, Juan Sepúlveda16, Wolfgang Wick17, Riccardo Soffietti18, James Perry19, Pierre Giglio20, Macarena De La Fuente21, Elizabeth Maher22, Andrew Bottomley23, Dan Zhao24, Shuchi Pandya24, Islam Hassan24, Lori Steelman24, Patrick Wen25, Timothy Cloughesy26
1Duke University Medical Center, 2Memorial Sloan Kettering Cancer Center, 3Erasmus Medical Center, 4Tel Aviv Medical Center, Tel Aviv University, 5Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne Université, 6University of California San Francisco, 7Huntsman Cancer Institute at the University of Utah, 8Davidoff Cancer Center at Rabin Medical Center, 9Toronto General Hospital, 10Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon, 11University of Michigan Comprehensive Cancer Center, 12University of Alabama at Birmingham, 13Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 14University Hospital of Lausanne, 15Kyoto University Graduate School of Medicine, 16Hospital Universitario 12 de Octubre, 17Universitätsklinikum Heidelberg, 18University of Turin, 19Sunnybrook Health Sciences Centre, University of Toronto, 20The Ohio State University Wexner Medical Center, 21Sylvester Comprehensive Cancer Center and Department of Neurology, University of Miami, 22University of Texas Southwestern Medical Center, 23Bottomley Consultants, 24Servier Pharmaceuticals, 25Dana-Farber Cancer Institute, 26University of California Los Angeles
Objective:
To evaluate the impact of vorasidenib on health-related quality of life (HRQoL), neurocognition and seizure activity.
Background:
The Phase 3 INDIGO study (NCT04164901) is a randomized, double-blind, placebo-controlled evaluation of vorasidenib, an oral, brain-penetrant mutant isocitrate dehydrogenase (mIDH) 1/2 inhibitor, in patients with grade 2 mIDH1/2 diffuse gliomas previously treated with surgery only. Vorasidenib showed statistically significant improvement in the primary and key secondary endpoints: image-based progression-free survival and time-to-next-intervention, respectively. Standard therapies of gliomas can contribute to patients experiencing neurocognitive deterioration and impairment of patients’ HRQoL; therefore, additional endpoints are reported to further characterize the clinical benefit of vorasidenib.
Design/Methods:
The secondary endpoint, HRQoL, was assessed by the Functional Assessment of Cancer Therapy – Brain (FACT-Br) questionnaire. Exploratory endpoints, neurocognition and seizure activity, were assessed by a validated battery of cognitive performance instruments and a patient diary, respectively. Patients with uncontrollable seizures were excluded.
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. Mean (standard deviation) FACT-Br total score (TS) was high at baseline in patients in both arms: 158.2 (26.40 [n=156]) for vorasidenib versus 158.8 (23.33 [n=143]) for placebo. At Cycle 13, FACT-Br TS was 163.3 (25.05 [n=78]) in patients on vorasidenib and 161.4 (23.60 [n=72]) in patients on placebo, demonstrating maintenance of HRQoL during the first 13 months of treatment with vorasidenib. Minor changes of neurocognitive function were observed in both arms up to Cycle 13, with no suggestion of a treatment effect. Frequency of patients self-reporting at least one seizure was similar in both arms through Cycle 13; at baseline, this was 20 patients in each arm.
Conclusions:
Treatment with vorasidenib was associated with preservation of HRQoL and neurocognition, and maintenance of seizure control.