Dr Moore on the Present Standing of PARP Inhibitors in Ovarian Cancer

“PARP inhibitors are most appropriate in a biomarker-selected population, [including] in patients with BRCA-mutated and/or HRD-positive disease.”

Kathleen N. Moore, MD, MS, associate director of clinical research at the Stephenson Cancer Center, the director of the Oklahoma TSET Phase I Program, and a professor in the Section of Gynecologic Oncology at Oklahoma University (OU) College of Medicine, OU Health, discussed the use of PARP inhibitors in patients with ovarian cancer.

Currently, PARP inhibitors are most appropriate for the treatment of patients in biomarker-selected populations, including those with BRCA-mutated disease and/or disease positive for homologous recombination deficiency (HRD), Moore began. There is a spectrum where some patients can achieve cure, but most do not; however, many patients experience long periods of disease-free survival with a time-limited use of a PARP inhibitor, she added. Patients who experience disease progression following treatment with a PARP inhibitor do not seem to have an impaired response to subsequent lines of therapy, including platinum-based regimens, although this is still being explored by investigators, she noted.

Patients with BRCA-mutated or HRD-positive ovarian cancer who experience disease progression during PARP inhibitor therapy are a population of interest for investigators and the progression is likely due to the biology of the tumor, Moore explained. Treatment with PARP inhibitors probably does not worsen the prognosis for these patients, but continued use of these agents could lead to the development of resistance mechanisms that could affect the response to future lines of therapy, she said. In the future, the granular molecular differences within patients with BRCA-mutated or HRD-positive ovarian cancer that could better inform treatment selection and sequencing with PARP inhibitors, she noted. This enhanced understanding could lead to the selection of other treatment options such as antibody-drug conjugates or CDK2 inhibitors, she concluded.