Combination Olaparib and Temozolomide for the Treatment of Glioma
Lauren Schaff, Marina Kushnirsky, Andrew Lin, Subhiksha Nandakumar, Christian Grommes, Alexandra Miller, Igor T. Gavrilovic, Craig Nolan, Elena Pentsova, Ingo K. Mellinghoff, Thomas Kaley
Abstract
<h3>Background and Objectives</h3> To report the tolerability and efficacy of olaparib with temozolomide (TMZ) for glioma. <h3>Methods</h3> Single-center retrospective series of patients with glioma treated with olaparib/TMZ from September 2018 to December 2021. <h3>Results</h3> 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/m<sup>2</sup> 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. <h3>Discussion</h3> 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. <h3>Classification of Evidence</h3> This case series provides Class IV evidence that treatment with olaparib/TMZ may result in radiographic response in patients with glioma.