Dr Tagawa on the Role of PARP Inhibitors in Prostate Cancer Treatment

Scott T. Tagawa, MD, MS, FACP, FASCO, professor of medicine and urology at Weill Cornell Medicine, and an attending physician at NewYork-Presbyterian–Weill Cornell Medical Center, discusses the current standing of PARP inhibitors in the treatment paradigm of metastatic castration-resistant prostate cancer (mCRPC).

There is not much debate on the utility of PARP inhibitors for patients with germline or somatic genomic alterations, particularly among those with BRCA2 alterations, Tagawa begins. However, there is some debate among clinicians about whether these therapeutics can be used to treat all patients with metastatic non-castrate prostate cancer and there are several clinical trials that are ongoing which aim to answer this question, Tagawa continues. Androgen receptor (AR) inhibitors in combination with PARP inhibitors are approved for treatment but these regimens are generally indicated for genomically selected patients who have not undergone prior treatment with an AR inhibitor; however, the number of patients with mCRPC who have not been exposed to an AR inhibitor is shrinking, Tagawa notes.

Clinicians are developing approaches and combination regimens with PARP inhibitors to improve the efficacy of other agents and allow PARP inhibition to be effective in an unselected population of patients with mCRPC, Tagawa says. Outside of AR inhibitors, PARP inhibitors are being combined with immunotherapy and radiation, including radionuclides, external beam radiation, and lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly 177Lu-PSMA-617), Tagawa explains. Studies combining PARP inhibition with radiation approaches are generally designed to improve the efficacy of the radionuclide by damaging DNA with the radiation and inhibiting repair with the PARP inhibitor, which could prove to be effective in a population of patients that is not as strictly selected, Tagawa notes.

Immunotherapy plus PARP inhibition has a sound rationale but has not produced significantly positive results to date, Tagawa says. This includes findings from a phase 3 clinical trial in patients with pretreated disease who did not experience a significant benefit over second-line AR therapy, Tagawa concludes.