Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear.
We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist.
Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease.
Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.
International journal of clinical oncology. 2024 Apr 06 [Epub ahead of print]
Akihiro Matsukawa, Pawel Rajwa, Tatsushi Kawada, Kensuke Bekku, Ekaterina Laukhtina, Jakob Klemm, Benjamin Pradere, Keiichiro Mori, Pierre I Karakiewicz, Takahiro Kimura, Piotr Chlosta, Shahrokh F Shariat, Takafumi Yanagisawa
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Canada., Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Jagiellonian University, Medical College, Krakow, Poland., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Wahringer Gurtel 18-20, 1090, Vienna, Austria. .