Advancing Homologous Recombination Repair Mutation Testing in Prostate Cancer in Australia: Shifting the Focus to Hormone Sensitive Prostate Cancer

Homologous recombination repair (HRR) gene alterations are key drivers of disease in prostate cancer. This has led to great interest in HRR targeted therapies, particularly polyadenosine diphosphate-ribose inhibitors (PARPi), in the treatment of metastatic castrate resistant prostate cancer (mCRPC). HRR alterations are typically early events in prostate cancer tumorigenesis. As a result, clinical trials are investigating the efficacy of PARPi therapy in metastatic hormone sensitive prostate cancer (mHSPC). Recently, based on positive results from the phase III AMPLITUDE trial, niraparib was approved in the United States for the treatment of patients with BRCA2-mutated mHSPC. Positive results have also recently been obtained from the phase III TALAPRO-3 trial; talazoparib added to enzalutamide led to significantly better imaging-based progression-free survival than placebo plus enzalutamide among patients with mHSPC harboring HRR alterations. Furthermore, international guidelines now recommend HRR mutation testing for patients with mHSPC. However, in Australia there is currently no reimbursement for HRR mutation testing in the mHSPC setting. Here, we review the current knowledge of the clinical relevance of HRR alterations and highlight the benefits of genomic profiling of hormone-sensitive disease prior to the development of castrate resistant disease.