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Published on: March 6, 2018
Do Older Patients With Metastatic Hormone-Sensitive Prostate Cancer Benefit From Triplet or Doublet Therapy? A
Susu Zhou1, Parissa Alerasool2, Noriko Kishi3
1Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Morningside-West, New York, NY; Division of Hematology and Medical Oncology, Department of Medicine, SUNY Upstate Medical University, Syracuse, NY.
Introduction:
With the expanded approval of androgen receptor axis-targeted (ARAT) agents, clinicians now have more treatment options to offer patients with metastatic hormone-sensitive prostate cancer (mHSPC). Uncertainty remains as to whether older population could benefit similarly from these intensification treatment options.
Patients And Methods:
A systematic database search was performed for randomized controlled trials (RCTs) evaluating the efficacy of androgen deprivation therapy (ADT) in combination with ARAT agents and/or docetaxel in older patients (aged ≥ 70 or 75 years) with mHSPC. The primary endpoint was overall survival (OS). Indirect comparisons of available treatment options were estimated using a random-effects network meta-analysis.
Results:
A total of 11 RCTs were eligible. In comparison with ADT alone or ADT + docetaxel doublet, darolutamide + ADT + docetaxel showed a significant OS benefit, with hazard ratios (HRs) of 0.47 (95% confidence interval [CI]: 0.28-0.77) and 0.61 (95% CI, 0.40-0.93), respectively. However, another triplet (abiraterone + ADT + docetaxel) failed to demonstrate a statistically significant OS benefit, with HRs of 0.61 (95% CI, 0.37-1.02) and 0.80 (95% CI, 0.52-1.24), respectively. Triplet therapies comprising darolutamide and abiraterone ranked first and second, with P score of .90 and .67, respectively, followed by darolutamide + ADT (0.61), apalutamide + ADT (0.60), enzalutamide + ADT (0.56), ADT + docetaxel (0.40), abiraterone + ADT (0.20) and ADT alone (0.06). Furthermore, our data suggest an additional benefit from adding docetaxel as a component of doublet and triplet therapies for older men with mHSPC.
Conclusion:
In older patients with mHSPC, triplet therapy comprising darolutamide, ADT, and docetaxel demonstrated the most pronounced OS benefit and ranked highest among currently available treatment options. Further studies are needed to explore the specific toxicities associated with the triplet regimen in this population to better balance oncologic benefits with treatment-related toxicities when making treatment decision.
Insights
For older men with metastatic hormone-sensitive prostate cancer, triplet therapy with darolutamide, androgen deprivation therapy, and docetaxel significantly improves overall survival. This combination therapy offers the most pronounced benefit among current treatment options for this population.
Area of Science:
- Oncology
- Clinical Pharmacology
Background:
- Expanded approval of androgen receptor axis-targeted (ARAT) agents provides new treatment options for metastatic hormone-sensitive prostate cancer (mHSPC).
- Clinical benefit of intensified treatment strategies in older mHSPC patients remains uncertain.
Purpose of the Study:
- To evaluate the efficacy of androgen deprivation therapy (ADT) combined with ARAT agents and/or docetaxel in older mHSPC patients.
- To compare different treatment intensification strategies for overall survival (OS) in this specific demographic.
Main Methods:
- Systematic literature search for randomized controlled trials (RCTs) in patients aged ≥70 or 75 years with mHSPC.
- Network meta-analysis to indirectly compare efficacy of ADT combined with ARAT agents and/or docetaxel.
- Primary endpoint assessed was overall survival (OS).
Main Results:
- The triplet therapy of darolutamide + ADT + docetaxel demonstrated a significant OS benefit compared to ADT alone (HR: 0.47) and ADT + docetaxel (HR: 0.61).
- Abiraterone + ADT + docetaxel did not show a statistically significant OS benefit.
- Darolutamide-based triplet therapy ranked highest in efficacy (P-score: .90), indicating superior outcomes in older mHSPC patients.
Conclusions:
- Triplet therapy with darolutamide, ADT, and docetaxel is the most effective treatment option for older patients with mHSPC, showing the greatest OS benefit.
- Further research is required to assess the specific toxicities of triplet regimens in this population to optimize treatment decisions.
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