Dr. McCann on Combination Trials With PARP Inhibitors in Ovarian Cancer

Kelly McCann, MD, PhD, a medical oncologist in the Breast Cancer Research Group at the University of California, Los Angeles, discusses combination trials of PARP inhibitors in patients with ovarian cancer.

PARP inhibitors seem to work best in the BRCA1/2 population, but they can also work in any patient who has homologous recombination repair deficiency. Homologous recombination is a type of DNA repair that repairs DNA double strand breaks. Clinical trials have tried to look at combining PARP inhibitors with chemotherapy. When they are combined, McCann states that they both tend to have myelosuppressive toxicities, giving patients anemia, thrombocytopenia, and neutropenia.

Most of these trials, McCann states, have started at full dose chemotherapy and escalated the PARP inhibitor. Many of these trials have not given patients the full therapeutic dose. Therefore, other combination strategies that don’t have overlapping toxicities have been explored. These include combinations with angiogenesis inhibitors that can induce a BRCA-like state in the cells. Bevacizumab (Avastin) and cediranib are 2 such agents that are currently in ongoing trials.