PARP Inhibitors in Ovarian Cancer

Evidence for Maintenance and Treatment Strategies

Antonio Bahena-González; Alfredo Toledo-Leyva; Dolores Gallardo-Rincón

Disclosures

Chin Clin Oncol. 2020;9(4):51 

In This Article

Conclusions and Future Directions

For many years, cytoreductive surgery and chemotherapy were the only treatment options for ovarian cancer. The addition of antiangiogenic therapy improved patient outcomes, but no clear effect on survival has been demonstrated. The recent addition of PARP inhibitors to the systemic treatment options has clearly caused a paradigm shift in ovarian cancer management. Olaparib, niraparib and rucaparib are approved by regulatory agencies for ovarian cancer treatment. As previously mentioned, these drugs have been rapidly moving in to the first line setting. Genetic testing for BRCA and HR- deficiency alterations has allowed better personalization of treatment, but selection of the best candidates continues to be a challenge. Many studies evaluating the optimal application of PARP inhibitors in medical practice are in progress.

The combination of PARP inhibitors and immunotherapy is currently under active investigation. Mutations generated after alterations of the DNA damage response mechanisms can originate neoantigens. Neoantigens are optimal targets for immunotherapy. Early phase clinical trials testing the combination of PARP inhibitors plus immunotherapy in ovarian cancer patients have showed some promising results.[47,48] At least three phase III studies are evaluating the benefits of this strategy (NCT03602859, NCT03737643 and NCT03522246).

Another issue that needs to be established is the efficacy of retreatment. In patients with recurrence after having received a PARP inhibitor, it is possible that sensitivity to PARP inhibitors might be retained after subsequent lines of cytotoxic treatment. A phase III trial that will try to confirm this assumption is being conducted (NCT03106987).

Other PARP inhibitors are also being tested in ovarian cancer patients (e.g., veliparib, talazoparib). VELIA was the first phase III study that focused on the efficacy and safety of the combination of a PARP inhibitor (veliparib) and chemotherapy.[49] Other ongoing trials are exploring this combination strategy.

Most toxicities observed with PARP inhibitors are relatively mild and require only observation or standard supportive care.

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