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Systemic Treatment for Metastatic Hormone Sensitive Prostate Cancer: A Comprehensive Meta-Analysis Evaluating Efficacy and Safety in Specific Sub-Groups of Patients - Beyond the Abstract

Patients with metastatic hormone-sensitive prostate cancer (mHSPC) represent a minority of metastatic prostate cancer patients. Despite this, several efforts have been done to detect effective systemic treatment in this setting. This is mainly due to the significant worse clinical outcomes related to mHSPC.1 Docetaxel, abiraterone, enzalutamide, and apalutamide have been assessed in different Phase III clinical trials and represent a concrete hope for these patients.2-11 However, due to a significant difference in terms of trial design some precious data about the clinical performance of these agents in a specific subgroup of patients may not be obvious.
In our systematic review and meta-analysis, we focused our attention on a specific subgroup of patients with mHSPC. We identified a specific subgroup of patients who may present the worst survival with:

1) docetaxel (patients aged ≥ 70 years, high Gleason score at diagnosis, and higher LDH serum levels)
2) abiraterone + prednisone (low Gleason score)
3) apalutamide/enzalutamide (visceral metastases, previously or concomitant docetaxel- exposed patients, high LDH serum levels)

The main limitation of this finding is related to the heterogeneous population enrolled in these Phase III studies and in the lack of inclusion of some of these variables in a pre-planned subgroup analysis, as known disease volume and risk of the disease should drive therapeutic choice between abiraterone or docetaxel. Our findings suggest that at least other clinical and pathological variables should be considered for an adequate treatment choice. The toxicity profile of each agent should be another element to assess before treatment choice. In our analysis, we confirmed the well known hematological and neurological toxicity of docetaxel in association with cardiological toxicity linked to abiraterone.

In conclusion, we did not consider two important issues represented by the quality of life assessment and the economic toxicity of these agents. Future studies should assess these elements and provide key data by which to ponder our decision in daily clinical practice.

Written by: Francesco Massari, MD, PhD, Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
References:

  1. Mosillo, Claudia, Roberto Iacovelli, Chiara Ciccarese, Emanuela Fantinel, Davide Bimbatti, Matteo Brunelli, Iolanda Bisogno et al. "De novo metastatic castration sensitive prostate cancer: State of art and future perspectives." Cancer treatment reviews 70 (2018): 67-74.
  2. Gravis, Gwenaelle, Karim Fizazi, Florence Joly, Stéphane Oudard, Franck Priou, Benjamin Esterni, Igor Latorzeff et al. "Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial." The lancet oncology 14, no. 2 (2013): 149-158.
  3. Gravis, Gwenaelle, Jean-Marie Boher, Florence Joly, Michel Soulié, Laurence Albiges, Franck Priou, Igor Latorzeff et al. "Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial." European urology 70, no. 2 (2016): 256-262.
  4. Sweeney, Christopher J., Yu-Hui Chen, Michael Carducci, Glenn Liu, David F. Jarrard, Mario Eisenberger, Yu-Ning Wong et al. "Chemohormonal therapy in metastatic hormone-sensitive prostate cancer." New England Journal of Medicine 373, no. 8 (2015): 737-746.
  5. Kyriakopoulos, Christos E., Yu-Hui Chen, Michael A. Carducci, Glenn Liu, David F. Jarrard, Noah M. Hahn, Daniel H. Shevrin et al. "Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial." Journal of Clinical Oncology 36, no. 11 (2018): 1080.
  6. James, Nicholas D., Matthew R. Sydes, Noel W. Clarke, Malcolm D. Mason, David P. Dearnaley, Melissa R. Spears, Alastair WS Ritchie et al. "Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial." The Lancet 387, no. 10024 (2016): 1163-1177.
  7. Fizazi, Karim, NamPhuong Tran, Luis Fein, Nobuaki Matsubara, Alfredo Rodriguez-Antolin, Boris Y. Alekseev, Mustafa Özgüroğlu et al. "Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer." New England Journal of Medicine 377, no. 4 (2017): 352-360.
  8. James, Nicholas D., Johann S. de Bono, Melissa R. Spears, Noel W. Clarke, Malcolm D. Mason, David P. Dearnaley, Alastair WS Ritchie et al. "Abiraterone for prostate cancer not previously treated with hormone therapy." New England Journal of Medicine 377, no. 4 (2017): 338-351.
  9. Chi, Kim N., Neeraj Agarwal, Anders Bjartell, Byung Ha Chung, Andrea J. Pereira de Santana Gomes, Robert Given, Álvaro Juárez Soto et al. "Apalutamide for metastatic, castration-sensitive prostate cancer." New England Journal of Medicine 381, no. 1 (2019): 13-24.
  10. Davis, Ian D., Andrew J. Martin, Martin R. Stockler, Stephen Begbie, Kim N. Chi, Simon Chowdhury, Xanthi Coskinas et al. "Enzalutamide with standard first-line therapy in metastatic prostate cancer." New England Journal of Medicine 381, no. 2 (2019): 121-131.
  11. Armstrong, Andrew J., Russell Z. Szmulewitz, Daniel P. Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Arun Azad, Antonio Alcaraz et al. "ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer." Journal of Clinical Oncology 37, no. 32 (2019): 2974-2986.
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