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Updated: Aug 8, 2025

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First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer: A Living Systematic Review

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Summary
This summary is machine-generated.

Triplet therapy shows improved overall survival in metastatic castration-sensitive prostate cancer (mCSPC) compared to docetaxel plus androgen deprivation therapy (ADT). However, benefits vary by disease volume and specific androgen pathway inhibitor (API) doublet comparisons.

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Area of Science:

  • Oncology
  • Clinical Trials
  • Prostate Cancer Research

Background:

  • The comparative effectiveness of triplet therapy versus androgen pathway inhibitor (API) doublets in metastatic castration-sensitive prostate cancer (mCSPC) remains unclear.
  • Understanding treatment efficacy across diverse patient subgroups is crucial for optimizing mCSPC management.

Purpose of the Study:

  • To compare the effectiveness of contemporary systemic treatments for mCSPC, including triplet and doublet regimens.
  • To analyze treatment outcomes across clinically relevant subgroups, such as high-volume and low-volume disease.

Main Methods:

  • Systematic review and meta-analysis of Phase 3 randomized clinical trials (RCTs) for first-line mCSPC treatment.
  • Data extracted from Ovid MEDLINE and Embase, with ongoing updates to include new evidence.
  • Fixed-effect network meta-analysis used to assess comparative effectiveness of overall survival (OS), progression-free survival (PFS), adverse events, and quality of life.

Main Results:

  • Ten RCTs involving 11,043 patients were analyzed.
  • Darolutamide (DARO) and abiraterone (AAP) triplets demonstrated improved OS compared to docetaxel (D) + androgen deprivation therapy (ADT) doublet in the overall population.
  • For high-volume disease, AAP + D + ADT showed improved OS versus D + ADT, but not versus other API doublets. In low-volume disease, AAP + D + ADT did not significantly improve OS over API doublets or D + ADT.

Conclusions:

  • Triplet therapy benefits in mCSPC require careful consideration of disease volume and specific doublet comparisons.
  • Findings suggest equipoise between triplet regimens and API doublet combinations, guiding future clinical trial design.
  • Further research is needed to fully elucidate the role of triplet therapy in different mCSPC patient subgroups.