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
Wei Chen, Soichiro Yoshida, Noriyoshi Miura, Shohei Fukuda, Yuma Waseda, Hajime Tanaka, Yasuhisa Fujii
Abstract
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.