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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer: A Living Systematic Review
Irbaz Bin Riaz1,2,3, Syed Arsalan Ahmed Naqvi2, Huan He4
1Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Importance:
The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown.
Objective:
To assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups.
Data Sources:
For this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database's inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a "living" auto search was created with weekly updates to identify new evidence as it became available.
Study Selection:
Phase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC.
Data Extraction And Synthesis:
Two independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022.
Main Outcomes And Measures:
Outcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life.
Results:
This report included 10 RCTs with 11 043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO + docetaxel [D] + androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP + D + ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D + ADT) but not compared with API doublets. Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT.
Conclusions And Relevance:
The potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.
Insights
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.
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.
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