The FDA approved the PARP inhibitor olaparib in December 2014 as a treatment for patients with BRCA-positive advanced ovarian cancer following treatment with three or more prior lines of therapy. This decision was based on a similar subpopulation of patients who experienced an objective response rate (ORR) of 34% in a single-arm phase II.
The phase II Study 19 trial assessed olaparib has maintenance therapy for patients with platinum-sensitive relapsed ovarian cancer, notes Bradley J. Monk, MD. Although this is not the approved indication, results from this study were positive. In patients with BRCA-mutant ovarian cancer, the median progression-free survival was 11.2 months with olaparib and 4.3 months with placebo (HR, 0.18; P <.0001).
Olaparib is administered at 400 mg twice daily until disease progression, Monk notes. However, toxicity may be another reason to discontinue treatment. Bone marrow suppression and anemia are minor toxicities associated with olaparib. Major treatment-limiting toxicities include gastrointestinal adverse events, such as dyspepsia, nausea, and diarrhea.
In order to proactively treat adverse events associated with olaparib, Monk recommends the administration of pantoprazole or an H2 receptor antagonist. Additionally, he advises that patients have access to ondansetron or loperamide, for nausea and diarrhea. In some situations, dose reductions may be required for patients on olaparib.
It is important to counsel patients ahead of time regarding the adverse events associated with olaparib, comments Robert L. Coleman, MD. In many situations, the gastrointestinal toxicities are often worst in the first cycle, adds Coleman.
Clinical trials are currently evaluating the benefits of combining PARP inhibitors with other biologic agents and chemotherapy, states Angeles Alvarez Secord, MD. The combination of a PARP inhibitor with chemotherapy has shown promising early activity, says Secord. Investigators are also evaluating whether increasing hypoxia with antiangiogenic agents or immunotherapies may be associated with a synergistic effect with PARP inhibitors.