Dr. Moore on Research Evaluating Repeat Exposure to PARP Inhibition in Ovarian Cancer

Kathleen Moore, MD, director, Oklahoma TSET Phase I Program, and associate professor, Section of Gynecologic Oncology, Stephenson Cancer Center, discusses research evaluating repeat exposure to PARP inhibition in patients with platinum-sensitive ovarian cancer.

In the prospective phase II Evolve study, Stephanie Lheureux, MD, and her colleagues took women who had progressed on a prior PARP inhibitor and evaluated one of the reported mechanisms of acquired resistance to PARP with combination therapy. One of the ways that patients develop resistance to PARP inhibition is upregulation of a pathway that restores homologous recombination proficiency (HRP). One of those pathways is VEGF.

Therefore, researchers believe that the combination of a PARP inhibitor with an antiangiogenic agent like bevacizumab (Avastin) or the TKI cediranib could overcome that acquired resistance, says Moore. Evolve was a small, translational science—driven study, in which investigators evaluated mechanisms of escape in platinum-sensitive, platinum-resistant, and unknown patients. Among 10 evaluable patients in each cohort, investigators noted some responses. Further data will be very important to apply to the design of the next phase of trials, Moore concludes.