PARP Inhibitor Tolerability and Impact on Progression-Free Survival in Patients with High-Grade, Ovarian Carcinoma with Brain Metastasis: A Case-Series

Brain metastases secondary to ovarian carcinoma is an uncommon but increasing phenomenon. PARP inhibitors (PARPi) are increasingly used as an adjunctive treatment in patients with central nervous system metastases (CNS). Historically brain metastases has a historically poor prognosis. Five women with a mean age of 60.4 ± 7.6 years were included. All had stage IIIC/IV ovarian cancer and diagnosed with brain metastases at recurrence. Three underwent resection for oligometastatic disease followed by post-operative stereotactic radiosurgery (SRS), one had SRS without surgery, and one patient underwent whole brain radiotherapy for multiple metastases. Pathology was confirmed in those who were resected. Two patients had evidence of systemic disease in addition to CNS spread. Three women were BRCA1/2 Positive. Following initial radiotherapy, one patient received adjuvant chemotherapy followed by olaparib maintenance, one received 13 cycles of bevacizumab/olaparib, followed by olaparib maintenance. A third patient was treated with olaparib/bevacizumab and two patients received olaparib monotherapy, both of whom continued on therapy. All received olaparib therapy during their treatment and all had minor dose modifications due to side effects. Mean survival from initial cancer diagnosis was 62.4 ± 20.4 months. Mean duration of PARPi therapy was 27.6 ± 16.8 months. Mean survival following CNS recurrence was 22.8 ± 12 months. One patient is disease-free, two patients are alive with stable disease, one patient is alive but off treatment secondary to progression, and one patient is deceased secondary to progression of her brain metastases after being on PARP therapy for 18 months. The cohort remained highly functional across the trajectory of their disease with ECOG scores of 1 (n=4) or 0 (n=1). The results of this single institution retrospective evaluation suggest olaparib in combination with radiotherapy +/- bevacizumab is well tolerated and can provide additional benefit in patients with brain metastases secondary to ovarian carcinoma