Dr. Moore on Treatment for Patients With Ovarian Cancer Who Develop Resistance to PARP Inhibitors

Kathleen Moore, MD, director, Oklahoma TSET Phase I Program, and associate professor, Section of Gynecologic Oncology, at Stephenson Cancer Center, discusses treatment options for patients with ovarian cancer who progress on a PARP inhibitor.

If a patient progresses on frontline maintenance therapy with a PARP inhibitor, the best indicator of subsequent response to PARP is still platinum sensitivity, says Moore. Therefore, if treating a patient who re-responded to platinum-based therapy, PARP inhibition as maintenance treatment may be tried again.

In terms of mechanisms of resistance, investigators demonstrated that patients in the phase II ARIEL2 trial who harbored BRCA reversion mutations in their circulating tumor DNA did not respond to rucaparib (Rubraca). These patients were PARP inhibitor—naïve, but they previously received platinum-based therapy, says Moore.

If a reversion mutation could be identified up front, it could indicate whether or not the patient should be put on a PARP inhibitor, a clinical trial with an alternative agent, or bevacizumab (Avastin). However, a commercially available assay has yet to be developed in that regard, concludes Moore.