The following is a summary of “Intensification Approaches and Treatment Sequencing in Metastatic Castration-resistant Prostate Cancer: A Systematic Review,” published in the September 2024 issue of Urology by Francini et al.
Recent advancements in treatment intensification have led to the approval of three novel combination therapies for metastatic castration-resistant prostate cancer (mCRPC). This systematic review synthesizes the emerging evidence on intensified treatment strategies for mCRPC and guides optimal therapeutic sequencing to enhance patient outcomes.
Following the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines, a thorough search was conducted across PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials.gov, and major international oncology conference proceedings up to May 15, 2024. The search focused on treatment intensification and sequencing strategies for mCRPC, identifying completed clinical trials and ongoing studies.
In total, 28 clinical trials and 24 ongoing studies were reviewed. This evidence was used to develop algorithms for optimal sequencing of approved treatments based on prior androgen receptor pathway inhibitor (ARPI) usage, with or without docetaxel, in earlier disease states. For first-line therapy, the combination of poly(ADP-ribose) polymerase (PARP) inhibitors with ARPIs has been shown to significantly improve radiographical progression-free survival (rPFS), particularly in patients with BRCA1/2 mutations. The AKT inhibitor ipatasertib, in combination with abiraterone also demonstrated extended rPFS in patients exhibiting PTEN loss or PIK3CA/AKT1/PTEN mutations. For patients with two or more risk factors for early progression on enzalutamide, the radionuclide therapy 177-Lu-PSMA-617 combined with enzalutamide has proven effective in prolonging progression-free survival. Furthermore, this review addresses ongoing research into intensification approaches and explores available and potential predictive and prognostic biomarkers that can guide treatment decisions.
The landscape of mCRPC treatment is rapidly evolving, driven by recent drug approvals and continued research into novel therapeutic combinations. To optimize patient outcomes, it is essential to improve individualized treatment strategies by incorporating genomic, molecular, and clinical predictors and prognostic indicators. This approach will ensure more precise and effective sequential use of available therapies, transforming the management of mCRPC.
Source: sciencedirect.com/science/article/abs/pii/S0302283824025995
