Dr Childs on Treatment Updates in mHSPC

Dan S. Childs, MD, medical oncologist, Mayo Clinic, discusses the evolution of the treatment armamentarium for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Historically, most patients with mHSPC have received doublet therapies, either androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) or ADT plus docetaxel, Childs says. In 2022, however, positive findings from the phase 3 ARASENS (NCT02799602) and PEACE-1 (NCT01957436) trials were published, which changed the mHSPC treatment landscape, Childs notes. ARASENS compared the triplet regimen of ADT plus docetaxel and darolutamide (Nubeqa) to the doublet regimen of ADT plus docetaxel. In this trial, treatment with the triplet regimen elicited a 32.5% reduction in the risk of death vs the doublet regimen (HR, 0.68; 95% CI, 0.57-0.80; P < .001). PEACE-1 compared the triplet regimen of ADT plus docetaxel and abiraterone to the doublet regimen of ADT plus docetaxel. In this trial, treatment with the triplet regimen led to a substantial reduction in the risk of death compared with the doublet regimen.

Although the findings from ARASENS and PEACE-1 were meaningful, they also spurred questions regarding the value that docetaxel adds to ADT and ARPI treatment backbones, Childs explains. However, this question may be difficult to answer, as no studies have been planned or conducted to compare the ARASENS and PEACE-1 triplet regimens with ARPI-based doublet regimens, Childs emphasizes.

In an OncLive^® Institutional Perspectives in Cancer webinar on genitourinary cancers, Childs and colleagues discussed data from a study conducted by Irbaz Bin Riaz, MBBS, MS, of Mayo Clinic, who conducted a mixed-method systematic review and meta-analysis of triplet regimens vs ARPI-based doublet regimens. This meta-analysis found that patients with de novo, high-volume mHSPC derive the most benefit from the addition of docetaxel to ADT and an ARPI, according to Childs. However, the oncologic benefit derived from receiving docetaxel early in the treatment course may be low for patients in other risk subgroups and not worth the risk of developing chemotherapy-associated adverse effects, Childs concludes.