No abstract

Purpose of review This article will review recent changes in the standard of care for olaparib, niraparib, and rucaparib, as well as ongoing trials evaluating this class of drugs in combination with antiangiogenic agents and PD-1/PD-L1 inhibitors. Recent findings Niraparib received FDA approval for use in patients with complete response or partial response to first-line platinum-based chemotherapy regardless of BRCAm or HRD status that was received in April 2020. FDA approval was received for olaparib in combination with bevacizamab for epithelial ovarian cancer patients with complete response/partial response to first-line chemotherapy and bevacizumab and g/sBRCA and/or genomic instability by Myriad myChoice CDx in May 2020. Summary In the last year, treatment with PARPi has extended to not only include BRCAm and HRD-deficient patients but also have shown improvement in outcomes in HRD-proficient patients. With these advancements, more patients can access these agents and receive benefit. In the upcoming years, it will be exciting to see the potential benefit when PARPs are added to other angiogenic antagonists and immunotherapy agents.

The poly ADP ribose polymerase olaparib is currently approved in front line BRCA-associated epithelial ovarian cancer (EOC), platinum-sensitive recurrence agnostic to BRCA status and for gBRCA as treatment in the fourth line and beyond. Women who are diagnosed with advanced stage EOC face a formidable challenge in overcoming their disease and achieving long-term, disease-free survival. The qualifier here is disease free. EOC is largely exquisitely chemosensitive, especially in the treatment naive (first line) setting and the expectation is that the vast majority of women will complete front line platinum-based chemotherapy with a response. When unselected (not selected by BRCA) women are enrolled on clinical trials, the response rate among those who have measurable disease at the time of chemotherapy initiation is 48% for carboplatin/paclitaxel and 67% for carboplatin/paclitaxel plus bevacizumab. When one considers the addition of women who start chemotherapy without measurable disease, they will likely also end chemotherapy without measurable disease and the overall rate of no evidence of disease at conclusion of chemotherapy approaches 80%. Despite this, the majority of women will suffer relapse of their disease, typically within the first 3 years following completion of therapy. Once recurrent, the disease is highly treatable for many years but no longer considered curable. This review will cover indications for olaparib in ovarian cancer as well as ongoing combination trials and rationale for these combinations.