Indian Journal of Urology (Jan 2022)

Combination therapy in metastatic castration sensitive prostate cancer: A Systematic review and network meta-analysis

  • Jatinder Kumar,
  • Muhammad Umar Alam,
  • Seyed Behzad Jazayeri,
  • Karthik Tanneru,
  • Soroush Bazargani,
  • Charu Shastri,
  • Shiva Gautam,
  • Shahriar Koochekpour,
  • Sanjeev Shukla,
  • Mark Bandyk,
  • Joseph Costa,
  • K C Balaji

DOI
https://doi.org/10.4103/iju.iju_402_21
Journal volume & issue
Vol. 38, no. 3
pp. 220 – 226

Abstract

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Introduction: Studies directly comparing the different combination therapies offered to men with metastatic castration sensitive prostate cancer (mCSPC), are not available yet. This study was designed using the network meta-analysis (NMA) framework to provide a comparison of the different available options for the treatment of men with mCSPC. Methods: A systematic search was performed and the prospective randomized controlled trials reporting the overall survival (OS) or failure-free survival (FFS) were selected for review. A total of 14 studies were included in the NMA. Results: The addition of abiraterone, apalutamide, docetaxel, and docetaxel with zoledronic acid to the androgen deprivation therapy (ADT) demonstrated a significant improvement in the OS. In indirect comparison, abiraterone had a higher impact on the OS as compared to docetaxel (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.0–1.46) and docetaxel with zoledronic acid (HR: 1.31, 95% CI: 1.05–1.63) but not apalutamide. Furthermore, apalutamide was not different than docetaxel or docetaxel with zoledronic acid. There was a significant improvement in the FFS with the combination of abiraterone, apalutamide, docetaxel (HR: 0.61, 95% CI: 0.46–0.81), docetaxel with zoledronic acid (HR: 0.62, 95% CI: 0.43–0.9), and enzalutamide (HR: 0.39, 95% CI: 0.25–0.61) as compared to the ADT alone. Similar to the indirect comparison of OS, abiraterone outperformed docetaxel (HR: 1.66, 95% CI: 1.12–2.47), docetaxel with zoledronic acid (HR: 1.69, 95% CI: 1.06–2.68), and enzalutamide (HR: 1.06, 95% CI: 0.63–1.80), but not apalutamide in terms of impact on the FFS. Conclusion: Overall, abiraterone demonstrated better OS and FFS outcomes as compared to all the other combination strategies in this NMA.