The Growing Role of PARP Inhibitors in Ovarian Cancer
Clinical trials are now evaluating the potential combination of PARP inhibitors with immunotherapy or other agents in patients with ovarian cancer.
With 3 PARP inhibitors approved by the FDA for use as frontline maintenance in patients with BRCA1/2-mutated ovarian cancer as well as in the recurrent setting, researchers continue to evaluate the role of this class of drugs in the treatment paradigm and how their use may be expanded, according to Robert L. Coleman, MD, FACOG, FACS.
One such inhibitor, rucaparib (Rubraca), received approval in April 2018 as a maintenance treatment for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy based on data from the phase III ARIEL3. Median progression-free survival (PFS) was 10.8 months with rucaparib versus 5.4 months with placebo. The overall response rate with rucaparib was 18%. In those with either germline or somatic BRCA mutations, a 77% reduction in the risk of progression or death was reported with rucaparib compared with placebo (HR, 0.23; 95% CI, 0.16-0.34; P <.0001).
Many of the toxicities observed with the agent are similar to those observed with the other 2 FDA-approved PARP inhibitors: olaparib (Lynparza) and niraparib (Zejula). The most common associated toxicities observed with the agent are gastrointestinal (GI) events as well as fatigue, according to Coleman. However, the hematologic toxicities observed with rucaparib may slightly differ from what is seen with the other PARP inhibitors, Coleman added. Rucaparib is now being examined in combination with other agents in ongoing trials.
“Rucaparib was 1 of these 3 PARP inhibitors that has a similar effect in respect to inhibition of the catalytic activity of PARP,” said Coleman, a professor and Ann Rife Cox Chair in Gynecology, in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, at The University of Texas MD Anderson Cancer Center. “The agent was initially studied in patients who carried a BRCA mutation, as well as those who had a vulnerability identified via a loss of heterozygosity test.”
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