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

Background and objectives: To report the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma.

Methods: Single-center retrospective series of patients with glioma treated with olaparib/TMZ from September 2018 to December 2021.

Results: Twenty patients (median age: 42 years, median Karnofsky Performance Status: 90) received olaparib/TMZ for diagnoses of IDH-mutant oligodendroglioma (n = 5), IDH-mutant astrocytoma grade 2-3 (n = 4), IDH-mutant astrocytoma grade 4 (n = 7), or IDH-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 IDH-mutant grade 2-3 glioma. No responses were seen in patients with grade 4 IDH-mutant astrocytomas (0/5) or IDH-wildtype gliomas (0/3). Progression-free survival was 7.8, 1.3, and 2.0 months, respectively.

Discussion: Olaparib/TMZ resulted in objective radiographic response in 50% of evaluable patients with recurrent IDH-mutant grade 2-3 gliomas with encouraging progression-free survival and manageable toxicity. This supports a prospective trial of olaparib/TMZ for this population.

Classification of evidence: This case series provides Class IV evidence that treatment with olaparib/TMZ may result in radiographic response in patients with glioma.