ASCO 2022 | Prevalence of DDR alterations in patients with mHSPC enrolled in ARCHES: next steps

Arun Azad, MBBS, PhD, FRACP, Peter MacCallum Cancer Centre, Victoria, Australia, discusses the next steps of the post hoc analysis on the prevalence of DNA damage response (DDR) alterations in patients with metastatic hormone-sensitive prostate cancer (mHSPC) enrolled in the Phase III ARCHES (NCT02677896). The trial investigated enzalutamide in combination with androgen deprivation therapy (ADT) versus placebo plus ADT in patients with mHSPC. The post hoc analysis found a lower prevalence of DDR alterations in patients with mHSPC in ARCHES, compared with the 7–12% previously reported in patients with metastatic castration-resistant prostate cancer. The next steps may include the investigation of both germline and somatic alterations, exploring additional clinical trials to gain awareness of the frequency of DNA damage response DDR alterations within this patient population. As these are rare alterations, a pooled analysis across several trials may increase statistical power to explore the prognostic and predictive significance in regards to identifying hereditary alterations. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.