The evolving landscape of PARP inhibitors in castration-resistant prostate cancer: a spotlight on treatment combinations.

INTRODUCTION

PARP inhibition in prostate cancer has become a standard-of-care option for men with metastatic castration-resistant prostate cancer (mCRPC) with deficiency in homologous recombination repair (HRRd). The benefit varies based upon the characteristics of the PARP inhibitor used and the underlying HRR defect. Optimal patient selection remains a clinical challenge, and investigations are underway to identify effective combination therapies to expand the population that benefits.

AREAS COVERED

We review the clinical development of the FDA-approved PARP inhibitors olaparib and rucaparib. Additionally, we explore the status of other PARP inhibitors that remain experimental in prostate cancer, based upon review of published abstracts, articles, and clinicaltrials.gov. Most new studies, including phase 3 trials for talazoparib and rucaparib, involve combinations with novel androgen receptor signaling inhibitors. We review the landscape of emerging PARP inhibitor-based combination therapies.

EXPERT OPINION

For men with or mutations, olaparib has a clear role for early use in the disease course of mCRPC. For men with other HRR mutations, that benefit remains less well defined, particularly with the availability of other treatment choices. Ultimately, combination strategies are likely to be the best avenue for men without or mutations to be treated with PARP inhibition.