MP27-05: Efficacy and Safety of Darolutamide in Nonmetastatic Castration-resistant Prostate Cancer Patients With and Without Prior Local Therapy With Radical Prostatectomy or Radiotherapy

David Robert Siemens*, Kingston, Canada, Karim Fizazi, Villejuif, France, Neal D. Shore, Myrtle Beach, SC, Matthew R. Smith, Boston, MA, Jorge Ortiz, Whippany, NJ, Anja Schmall, Berlin, Germany, Shankar Srinivasan, Whippany, NJ, Frank Verholen, Basel, Switzerland, Matthias Saar, Aachen, Germany

Introduction: Darolutamide (DARO), a structurally distinct and highly potent androgen receptor inhibitor, significantly reduced the risk of metastasis by approximately 2 years and the risk of death by 31% versus placebo (PBO) and demonstrated a favorable safety profile in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the phase 3 ARAMIS trial (NCT02200614). In this post hoc analysis of ARAMIS, the efficacy and safety of DARO were evaluated in patients with nmCRPC with or without prior local therapy by radical prostatectomy (RP) or radiotherapy (RT) to determine if the impact of DARO on these patients was consistent or if prior local therapy altered the effects of DARO. Here, we report outcomes in the DARO treatment arm.

Methods: Patients with nmCRPC were randomized 2:1 to DARO or PBO while continuing androgen deprivation therapy (ADT). DARO patients who received prior RP or RT were compared with those who received neither therapy for overall survival (OS) and time to prostate-specific antigen (PSA) progression using adjusted Cox regression analysis. PSA response (=50% decline from baseline) and adverse events (AEs) were summarized by use of prior RP or RT.

Results: In ARAMIS, 43.6% (416/954) of DARO patients were treated with prior RP or RT. The treatment benefit of DARO on OS was consistent for patients on DARO with prior local therapy compared with patients on DARO with no prior local therapy. Median time to PSA progression in DARO-treated patients with prior local therapy was similar to those without prior local therapy (29.5 and 26.0 months; HR 0.96 [95% CI 0.77–1.20]). PSA response rates (=50% decline from baseline) were similar for patients with and without local therapy in the DARO arm (85.6%, 83.8%). For RP/RT-treated and RP/RT-untreated patients receiving DARO, similar incidences of any AEs (87.7%, 84.2%), grade 3/4 AEs (26.7%, 26.0%), and discontinuations due to AEs (7.7%, 9.9%) were reported.

Conclusions: The treatment benefit of DARO on OS and PSA outcomes was consistent for patients with and without prior local therapy with RP or RT. The safety and tolerability profile of DARO was similar across the two subgroups.

Source of Funding: Bayer AG and Orion Pharma