Dr. Hussain on Retrospective Analysis of the ARASENS trial in mHSPC

Maha H. Hussain, MD, FASCO, FACP, Genevieve E. Teuton professor of medicine, Division of Hematology Oncology, Department of Medicine, deputy director, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, discusses key efficacy and safety data from a secondary analysis of the phase 3 ARASENS trial (NCT02799602) in metastatic hormone-sensitive prostate cancer (mHSPC).

The randomized, placebo-controlled trial evaluated the addition of darolutamide (Nubeqa) to docetaxel and androgen deprivation therapy (ADT) vs docetaxel, ADT, and placebo in patients with mHSPC. In this trial, the experimental triplet regimen resulted in a statistically significant reduction in the risk of death by 32.5%, and consistent overall survival (OS) benefit across prespecified subgroups. Moreover, the incidence of treatment-related adverse events (TEAEs) was comparable between both groups. Based on these findings, the FDA approved the regimen for this population in August 2022.

A retrospective, secondary analysis of patient outcomes from the ARASENS trial was conducted to identify selected benefit for patients based on disease volume and risk status, Hussain says. Notably, the original trial did not stratify patients by these criteria, Hussain adds. Results showed that 77% of patients had high-volume disease and 70% had high-risk disease. These patients generally experience worse responses compared with patients with low-volume or low-risk status, Hussain explains. Additionally, the majority of patients had de novo metastatic disease, which is another poor prognostic factor, she says.

Overall, separation of the Kaplan-Meier curves indicated that the triplet regimen similarly prolonged OS regardless of risk or volume criteria, Hussain continues. Although this trend is promising, full data are unavailable due to the trial's termination, Hussain notes. Hazard ratios favored the experimental triplet vs the placebo regimen across subgroups, Hussain states.

Additionally, there was a trend towards improved time to castration resistance with the triplet regimen, Hussain details. This is a key end point, as castration-resistant tumors are considered terminal and associated with worse outcomes, Hussain elaborates. Lastly, there was no difference in the incidence of TRAEs in patients with high/low risk or high/low volume. This indicates that the treatment is well tolerated overall, Hussain concludes.

Editor's Note: Dr. Hussain reports serving as a consultant or in an advisory and leadership role for AstraZeneca, Bayer, Convergent Therapeutics, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Tempus; she received funding from Arvinas (Inst), AstraZeneca (Inst), Bayer (Inst), Genentech (Inst), PCCTC (Inst), Pfizer (Inst); she received honoraria from Astellas Pharma, AstraZeneca, Clinical Care Options, Great Debates and Updates, Medscape Zero, Merck, Precisca, Targeted Oncology, UroToday; she reports affiliation with a patent application from Exelexis, Inc.