This series of videos has been developed by myself, Professor Phil Cornford of Liverpool University Hospitals in the UK and Vice Chair of the EAU Prostate Cancer Guidelines Panel, in association with ecancer. The series looks at the current state of play in PARP inhibitor use in prostate cancer and what we might expect in the future. 

As well as being used as monotherapy after hormone therapy, PARP inhibitors are now being combined with novel hormone therapies which may result in a treatment benefit regardless of HRR status. Several ongoing studies are looking at the gaps in knowledge and understanding around PARP inhibitors’ use in prostate cancer, including use at an early stage in hormone-sensitive prostate cancer.

There is the potential to further refine patient selection by taking into account a wider range of biomarkers, and both genomic signature and functional tests could eventually become complementary tools to next generation sequencing for optimising patient selection for PARP inhibitor treatment.

As well as novel hormonal combinations such as androgen receptor signalling inhibitors, there is the potential for combination with immune checkpoint inhibitors, anti-VEGF therapies, and DNA damaging or other DDR targeting agents.

One of the major concerns related to targeted therapies is drug resistance. Even PARP inhibitors, which often show initial good responses, ultimately lose their effectiveness, leading to disease relapse. It’s hoped that these combinations may help tackle this issue. Further studies are also needed for better prognostic and predictive gene-signature based stratification of patients.

As well as the metastatic castration-resistant prostate cancer setting, trials are currently underway to look at PARP inhibitors in hormone sensitive prostate cancer. The trials shown are a mix of biomarker-selected and biomarker-unselected patients.