Efficacy of docetaxel addition to next‐generation androgen receptor‐axis‐targeted therapies and androgen deprivation therapy in metastatic hormone‐sensitive prostate cancer: A tumor volume‐specific analysis

Background The effectiveness of docetaxel in addition to next‐generation androgen receptor‐axis‐targeted therapies and androgen deprivation therapy (ADT) for metastatic hormone‐sensitive prostate cancer (mHSPC) remains unclear. We evaluated the efficacy of this combination through tumor volume‐specific analysis. Methods Individual patient data were reconstructed from seven clinical trials focusing mHSPC (ARASENS, PEACE‐1, TITAN, ENZAMET, ARCHES, STAMPEDE, and LATITUDE) through the Shiny method. Overall survival (OS), radiological progression‐free survival (rPFS), and time to castration‐resistant prostate cancer (CRPC) were analyzed in the overall cohort and tumor volume‐specific (high/low) subgroups. Sensitivity analyses were performed based on treatment methods and metastasis onset. Results In 6931 cases, adding docetaxel to ARAT and ADT did not significantly improve OS (hazard ratio [HR] = 1.07, 95% confidence interval [CI]: 0.95–1.22, p = 0.27), rPFS (HR = 0.88, 95% CI: 0.73–1.05, p = 0.16), or time to CRPC (HR = 0.97, 95% CI: 0.80–1.18, p = 0.74). High‐volume disease showed a non‐significant trend toward improved OS with the triplet regimen. Low‐volume disease showed a similar trend. Sensitivity analyses for second‐generation androgen receptor inhibitors indicated potentially less advantageous OS with docetaxel addition, but no significant differences when stratified by tumor volume. Analyses of the docetaxel‐naïve, abiraterone, and synchronous metastasis subgroups showed no statistically significant differences in OS compared with the overall population and volume‐stratified cases. Conclusions Patients with mHSPC did not show significant improvement with docetaxel addition to ARAT‐based regimens, regardless of tumor volume. Further research is needed to identify potential beneficiaries of this combination therapy.