Postprogression Survival of Patients with Metastatic Hormone-sensitive Prostate Cancer who Received Darolutamide or Placebo in Combination with Docetaxel and Androgen Deprivation Therapy: Post Hoc Analysis of the Phase 3 ARASENS Trial

Background and objective: Darolutamide + docetaxel + androgen-deprivation therapy (ADT) significantly improved overall survival (OS) and delayed time to disease progression versus docetaxel + ADT in ARASENS (NCT02799602). We report data on subsequent antineoplastic therapies received and associated OS after discontinuation of the study treatment. Methods: Patients were randomized 1:1 to darolutamide 600 mg orally twice daily or placebo, both with docetaxel + ADT. After treatment discontinuation, patients entered follow-up periods during which information on subsequent therapies and survival was collected. Postprogression OS was estimated using the Kaplan-Meier method as the time from initiation of first subsequent therapy to death and was compared in multivariable Cox regression analyses. Key findings and limitations: Of the 1305 patients treated, 315/651 who received darolutamide and 495/654 who received placebo entered follow-up, and 57% and 76% of these patients, respectively, received subsequent therapy. In the darolutamide group, first subsequent therapy was either an androgen receptor pathway inhibitor (ARPI; 63%) or a taxane (29%), and corresponding postprogression median OS was similar (13 vs 11 mo; hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.50–3.09). In the placebo group, first subsequent therapy was an ARPI in 78% and a taxane in 19% of cases, with worse OS for the taxane versus ARPI subgroup (14 vs 23 mo; HR 3.18, 95% CI 1.56–6.50). The main limitation of these analyses is their post hoc nature. Conclusions and clinical implications: For ARPI-naïve patients who did not receive darolutamide in ARASENS, postprogression survival was longer with subsequent ARPI versus taxane treatment, but OS remained shorter in comparison to the darolutamide group. Decisions on postprogression therapy should consider disease volume and drugs with different mechanisms of action.