Currently available post hoc phase 3 trial-derived data suggest better cancer-control outcomes in apalutamide-treated metastatic hormone-sensitive prostate cancer (mHSPC) patients achieving an (ultra)low prostate-specific antigen (PSA) nadir. This study aims to validate ultralow PSA nadir cutoffs.
Relying on an institutional prostate cancer database, 107 eligible patients were yielded. The currently available PSA nadir cutoffs (SWOG trial: <0.2 ng/ml; ultralow TITAN trial: ≤0.02 vs 0.02-0.2 vs >0.2 ng/ml) and PSA responses (≥99%) were tested for time to castration-resistant prostate cancer (ttCRPC) and overall survival (OS) in mHSPC patients treated with apalutamide. Finally, comparisons were made against abiraterone mHSPC treatment.
Overall, 107 mHSPC patients treated with apalutamide at a median age of 68 yr and baseline PSA of 29 ng/ml were included. The highest proportion of included patients (40.2%) achieved an ultralow PSA nadir of ≤0.02 ng/ml. Patients reaching the SWOG 9346-defined PSA nadir of <0.2 ng/ml and ultralow PSA nadir of ≤0.02 ng/ml harbored the longest time to metastatic castration-resistant prostate cancer (mCRPC) and OS (all p < 0.05). Moreover, 80% of mHSPC patients treated with apalutamide achieved a PSA response of ≥99%. These patients also harbored better time to mCRPC and OS outcomes, relative to patients with a <99% PSA response (both p < 0.05). In the second step of analyses, a comparison against abiraterone patients showed a significantly higher rate of achieving an ultralow PSA nadir of ≤0.02 ng/ml: 40.2% versus 8.8% for apalutamide versus abiraterone, resulting in a significantly longer ttCRPC for the apalutamide-treated (37 mo) than for the abiraterone-treated (22 mo) group (p = 0.001), even after multivariable adjustment and in sensitivity analyses for high-risk mHSPC patients only. The study is limited by its retrospective design.
In the real-world setting, most mHSPC patients treated with apalutamide achieve an ultralow PSA nadir, which is associated with better cancer-control outcomes. Moreover, a PSA response of ≥99% predicts better outcomes. In head-to-head comparisons, apalutamide achieves better PSA kinetics and ttCRPC outcomes than abiraterone.
A prostate-specific antigen (PSA) nadir of <0.02 ng/ml and PSA responses ≥99% are associated with better cancer-control outcomes in metastatic hormone-sensitive prostate cancer patients treated with apalutamide.
European urology oncology. 2024 Aug 31 [Epub ahead of print]
Mike Wenzel, Cristiana Cano Garcia, Clara Humke, Benedikt Hoeh, Thomas Steuber, Derya Tilki, Axel S Merseburger, Luis A Kluth, Felix K H Chun, Philipp Mandel
Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany. Electronic address: ., Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Koc University Hospital, Istanbul, Turkey., Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.