Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series.

Abstract

To report the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma. Single-center retrospective series of patients with glioma treated with olaparib/TMZ from September 2018 to December 2021. Twenty patients (median age: 42 years, median Karnofsky Performance Status: 90) received olaparib/TMZ for diagnoses of <i>IDH</i>-mutant oligodendroglioma (n = 5), <i>IDH-</i>mutant astrocytoma grade 2-3 (n = 4), <i>IDH</i>-mutant astrocytoma grade 4 (n = 7), or <i>IDH-</i>wildtype glioma (n = 4). One patient was treated upfront and 19 at recurrence (median = 3). Olaparib 150 mg was administered 3 times/week concurrent with TMZ 50-75 mg/m² daily. Fatigue, gastrointestinal symptoms, and hematologic toxicity were common. Six of 20 patients required dose reduction (n = 4) or discontinuation (n = 2) due to toxicity. Radiographic response was evaluable in 16 and observed (complete + partial) in 4/8 with <i>IDH</i>-mutant grade 2-3 glioma. No responses were seen in patients with grade 4 <i>IDH</i>-mutant astrocytomas (0/5) or <i>IDH</i>-wildtype gliomas (0/3). Progression-free survival was 7.8, 1.3, and 2.0 months, respectively. Olaparib/TMZ resulted in objective radiographic response in 50% of evaluable patients with recurrent <i>IDH</i>-mutant grade 2-3 gliomas with encouraging progression-free survival and manageable toxicity. This supports a prospective trial of olaparib/TMZ for this population. This case series provides Class IV evidence that treatment with olaparib/TMZ may result in radiographic response in patients with glioma.