ASCO GU 2018: Abiraterone or Docetaxel in Men with Metastatic Castration-sensitive Prostate Cancer: A Pooled Analysis of Castration Resistance-free Survival and Toxicity

San Francisco, CA (UroToday.com) The management of metastatic prostate cancer (PCa) continues to change in rapid succession. While we were once reliant on androgen-deprivation therapy for hormone-sensitive prostate cancer (hsPCa) and docetaxel alone for the treatment of metastatic castration-resistant PCa (mCRPC), the landscape of PCa treatment has drastically changed. The introduction of androgen axis targeting agents, specifically enzalutamide (ENZA) and abiraterone (ABI), have revolutionized the field.

Since their initial introduction as alternatives to docetaxel for mCRPC based on AFFIRM1/PREVAIL2 and COU-AA-3013 and 3024, docetaxel itself was promoted to first-line therapy for metastatic hsPCa, particularly in the setting of high-volume disease.5 Androgen axis inhibitors followed suit more recently, with the highly publicized results of LATITUDE6 and STAMPEDE7, which demonstrated significant survival benefit with the use of abiraterone in conjunction with ADT for metastatic hsPCa.

At this time, in the setting of metastatic hsPCa, the main treatment options are ADT alone, abiraterone + ADT or docetaxel + ADT. However, as the authors of this abstract note, none of these randomized trials have reported castration resistance-free survival (CFS) and toxicity data, both of which are clinically relevant outcomes for physicians and patients.

The authors completed a systematic review and meta-analysis to assess CFS and toxicity of adding Abi or Docetaxel to ADT in men with hsPCa. Subgroup analyses compared patients on A and D in terms of CFS.

Five total studies were included, after systematic review. The addition of Abi or Docetaxel to ADT, as expected from the PFS and OS data, decreased the risk of development of castration-resistance by 53% (5 studies, 4,462 participants, HR = 0.47, 95% CI 0.33-0.67). In a subgroup analysis, with regards to CFS, the addition of Abi seemed to be better than Docetaxel (5 studies, HR = 0.31, 95% CI 0.27-0.34 versus HR = 0.62, 95% CI 0.56-0.69, test for subgroup difference, p< 0.001). This highlights that starting patients on Abi actually lengthens the hsPCa stage of the disease, not just improving outcomes once they become castration-resistant.

Different profiles of toxicity were seen with Abi and Docetaxel, as expected due to their different mechanisms of action. While Abi increased the risk of hypokalemia (3,107 participants, HR = 6.63, 95% CI 3.5-12.5) and cardiac toxicity (3,107 participants, HR = 2.4, 95% CI 1.7-3.3), Docetaxel increased the risk of neutropenia (2,151 participants, HR = 13, 95% CI 8.9-18.8) and neuropathy (2,151 participants, HR = 2.25, 95% CI 1.18-4.3).

In this systematic review and meta-analysis, the authors demonstrate that Abi and Docetaxel, when added to ADT, increases CFS in men with hsPCa, with a longer CFS noted for Abi compared to Docetaxel. Considering CFS and OS, Abi may be preferred to Docetaxel as initial therapy – as sequencing of these medications has become the hot topic in the field. Toxicity profiles differed between Abi and Docetaxel and should be accounted for when deciding on treatment.

Speaker: Joelle Helou

Co-Authors: Charles N Catton, Glenn Bauman, Rouhi Fazelzad, Jacques Raphael

Institution(s): University of Toronto Princess Margaret Cancer Centre, Toronto, ON, Canada; Western University, London Regional Cancer Program, London, ON, Canada

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

References:

1. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187-1197.
2. Beer TM, Armstrong AJ, Rathkopf D, et al. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: Extended Analysis of the Phase 3 PREVAIL Study. Eur Urol 2017;71(2):151-154.
3. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13(10):983-992.
4. Rathkopf DE, Smith MR, de Bono JS, et al. Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol. 2014;66(5):815-825.
5. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.
6. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
7. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377(4):338-351.
8. Moreira DM, Freedland SJ, et al. Predictors of Time to Metastasis in Castration-resistant Prostate Cancer. Urology. 2016 Oct;96:171-176. doi: 10.1016/j.urology.2016.06.011. Epub 2016 Jun 16.
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