ASCO GU 2018: Influence of CHAARTED, STAMPEDE, and LATITUDE eligibility criteria on utilization of abiraterone and docetaxel

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. Yet, with varying adverse event profiles and differing costs, the authors of this study aimed to assess a real world population for eligibility. As the eligibility criteria varied in each of the phase III seminal manuscripts, they evaluated all patients for eligibility in CHAARTED, STAMPEDE and LATITUDE, with an aim to help facilitate decision making between abiraterone and docetaxel.

They identified 102 men with high-risk localized or metastatic hormone-naïve prostate cancer (HNPC) who were seen between 06/2014 to 09/2017 for consideration of additional systemic therapy secondary to CRPC progression. Following chart review for basic demographics and clinical features, the authors retrospectively applied the eligibility criteria of CHAARTED (both high-volume [HV] and low-volume [LV] definition), STAMPEDE, and LATITUDE to determine the rate of men qualifying for treatment with Abiraterone, Docetaxel, or both agents.

Of the 102 men, 98.0%, 69.6%, 28.4%, and 47.1% of men fulfilled the STAMPEDE, CHAARTED-HV, CHAARTED-LV, and LATITUDE criteria, respectively. As abiraterone funding for HNPC therapy is still pending in Ontario and that docetaxel funding is limited to men with CHAARTED-HV disease, the rate of docetaxel therapy was 62.0%, 69.0%, and 77.1% of patients who met the STAMPEDE, CHAARTED-HV, and LATITUDE criteria, respectively. 42 of 48 men (87.5%) conforming to LATITUDE would also be candidates for docetaxel, whereas 42 of 71 CHAARTED-HV patients (59.2%) would be eligible for abiraterone as alternative treatment.

Based on this, while all men fulfilling the STAMPEDE criteria (100 of 102, 98%) could be considered for either agent, only 42 of 102 patients (41.2%) would be candidates for both of the drugs if the CHAARTED-HV and LATITUDE criteria were applied.

As such, regardless of health care system, due to the broader inclusion criteria of STAMPEDE, applying the more restrictive CHAARTED-HV and LATITUDE criteria would result in around 30% or 50% fewer men being offered docetaxel or abiraterone secondary to ADT, respectively. In addition, only around 40% of men would conform to both CHAARTED-HV and LATITUDE, and thus be candidates for both drugs.

Limitations / Discussion Points:
1. Ontario / Canadian funding differs from the United States and other countries. Hence, the generalizability regarding funding implications is limited.
2. This is a highly selected population being referred to a tertiary care center – the distribution of patients may reflect this specialized population.

Presented by: Shruti Parshad

Co-Author: Urban Emmenegger 

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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