gms | German Medical Science

Background: Recently, two randomized controlled trials demonstrated an overall survival benefit for triplet therapy (ARAT&docetaxel&ADT) over doublet therapy (docetaxel&ADT), hereby broadening the treatment for metastatic hormone-sensitive prostate cancer (mHSPC) fundamentally. We previously performed a systematic review and network meta-analysis investigating the role of triplet therapy vs. doublet therapy (focusing on ARAT&ADT, as this is the actual standard of care in many countries) for mHSPC. However, survival data according to disease volume was only available for one triplet therapy regimen (PEACE-1). Most recently, survival data stratified according to disease volume for the second triplet therapy (ARASENS) have been presented.

Objective: To rank therapy options (Triplet vs. doublet [docetaxel&ADT] vs. doublet [ARAT&ADT]) and address them within formal network meta-analysis (NMA) following stratification according to (a) low- and high-volume tumor burden and (b) doublet vs. triplet therapy.

Results: Consistent with previous findings, ADT alone does not represent a valid treatment option anymore in mHSPC. Similar considerations apply to doublet therapy with docetaxel&ADT. In low volume mHSPC, the benefit of combination therapies (Reference: ADT) other than ARAT&ADT was not substantial. Contrarly in high volume, darolutamide&docetaxel&ADT ranked first (HR: 0.50; 95% – CI: 0.40–0.63; P-score: 0.92), abiraterone&docetaxel&ADT ranked second (HR: 0.52; 95% – CI: 0.38–0.71; P-score: 0.85) followed by ARAT&ADT combination therapies. Noteworthy in high volume mHSPC, solely the triplet therapy darolutamide&docetaxel&ADT demonstrated superior overall survival data (HR: 0.76; 95% – CI: 0.59–0.97) compared to (pooled) ARAT+ADT.

Conclusion: The results of the updated network meta-analysis underline the role of triplet therapy in the setting of high-volume mHSPC. More mature data are needed to draw reliable conclusions for the specific subset of low volume mHSPC.