A multicenter retrospective study of the duration of adjuvant temozolomide in IDH-mutant gliomas.

Abstract

e14048 Background: Gliomas with isocitrate dehydrogenase (IDH) mutations have improved prognosis and are more treatment responsive compared to IDH wild-type gliomas. For glioblastoma (IDH wild-type glioma), Stupp protocol has demonstrated superiority with 6 cycles of adjuvant temozolomide (TMZ). However, recommended duration of TMZ for IDH mutant gliomas is not well-defined, with studies such as RTOG 0424, CATNON, and CODEL extending treatment up to 12 cycles. Prolonged TMZ duration following radiation therapy (RT) is associated with increased toxicity including both financial (cost of drug, lab work, and visits) and drug side effects including cytopenias. We aimed to evaluate for any differences in survival between patients treated with more than 6 cycles of TMZ and those treated with 6 or fewer. Methods: We conducted a multicenter retrospective study of patients treated at the University of Washington and Stanford Medical Center for oligodendrogliomas (oligo) and IDH mutated astrocytomas (astro) using World Health Organization 2016 molecular diagnostic criteria including IDH mutation. Other inclusion criteria were grades 2 and 3, as well as treatment with RT (with or without concurrent TMZ) followed by adjuvant TMZ monotherapy with number of cycles documented. Survival probability, mean overall survival (mOS) and mean progression-free survival (mPFS), were calculated using Kaplan-Meier method with distributions compared using log-rank test in Prism GraphPad comparing >6 cycles of adjuvant TMZ and ≤6 cycles. Results: Of 153 patients treated with both XRT and adjuvant TMZ, 88 were treated with between 1 and 6 cycles of adjuvant TMZ, while 91 were treated with >6 cycles Treatment duration ranged from 1-12 cycles for oligos, 4-12 cycles for grade 2 astros, and 1-14 cycles for grade 3 astros. mOS of oligos was undefined for those treated with 1-6 cycles and 84 months (m) for those treated with >6 cycles (p=0.1448). mOS of grade 2 astros was 154m for those treated with 1-6 cycles and 162.9m for those treated with >6 cycles (p=0.8864). mOS of grade 3 astros was undefined for those treated with 1-6 cycles and 117m for those treated with >6 cycles (p=0.8003). mPFS of oligos was 93m for those treated with 1-6 cycles and undefined for those treated with >6 cycles (p=0.584). mPFS of grade 2 astros was 79.6m for those treated with 1-6 cycles and 144.56m for those treated with >6 cycles (p=0.610). mPFS of grade 3 astros was 72m for those treated with 1-6 cycles and 79.4m for those treated with >6 cycles (p=0.9596). Conclusions: While this study is limited by power, there was no difference in mOS or mPFS with greater than 6 cycles of TMZ among patients with oligodendrogliomas and IDH mutant astrocytomas. More data is needed to evaluate the optimal treatment duration to maximize survival without over-exposing these patients to toxicities.[Table: see text]