ASCO 2019: Suppression of Testosterone Production Using Abiraterone Acetate with or without Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer

Chicago, IL ( Cougar 301 and Cougar 302 established the role of abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC), both before and after chemotherapy.1,2 For patients after chemotherapy, abiraterone improved median overall survival over placebo by 3.9 months (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). For patients before chemotherapy, abiraterone improved median overall survival over placebo by 8.2 months (16.5 months vs 8.3 months, HR 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). In both of these studies, patients were also on continuous androgen deprivation therapy. However, it is unknown if patients require the continuous androgen blockade in the setting of abiraterone, a cytochrome P450 17-alpha-hydroxylase/C17,20 lyase (Cyp17)-inhibitor. This abstract (5049), along with another abstract at this meeting (5046), provide some data to shed more light on the efficacy of abiraterone without continuous LHRH therapy.

This abstract provides data on 57 patients who either received abiraterone + androgen deprivation therapy (ADT) or abiraterone alone for mCRPC. Unlike the abstract by Carsten H. Ohlmann, MD et al, this was a non-randomized, retrospective review of patients.
The majority of patients received abiraterone + ADT (36), 10 patients received abiraterone alone, and 11 patients transitioned from the combination to abiraterone alone. Testosterone levels were measured 235 times amongst all patients and was undetectable (<2 ng/dL) in the majority of patients (134/152, 88%) on the combination therapy as well as on abiraterone alone (86/99, 87%). For those patients with testosterone levels >2 ng/dL, no patients in the combination arm had testosterone greater than 30 ng/dL, and 1 patient in the abiraterone alone arm had a testosterone level above 30 ng/dL.
Cost analysis was conducted in this study with the price of leuprolide injection set at $5252.86 for a 3-month injection. Based on that assumption, this study estimated that omission of leuprolide would have resulted in a cost savings of $1.29 million. Furthermore, now that abiraterone is used in the metastatic castration sensitive setting based on data from STAMPEDE and LATITUDE, exclusion of leuprolide in an earlier setting may prove even more cost-effective.
The authors here examine the ability of abiraterone to suppress testosterone alone without leuprolide. This was a non-randomized study with a very small cohort of patients, but it nevertheless provides thought-provoking data regarding the use of abiraterone alone without the addition of leuprolide. For this practice to shift to the standard of care, larger randomized studies are necessary to demonstrate that ADT + Abiraterone is equivalent to Abiraterone alone. From a cost-effectiveness standpoint, the healthcare system would save $20,000 every year for a patient who is on single agent abiraterone without leuprolide based on the cost assumptions by the authors, which could translate to significant savings for patients who are on abiraterone in the metastatic hormone-sensitive prostate cancer (mHSPC) setting.

Presented by: Gautam Gopalji Jha, MBBS, MS, University of Minnesota, Minneapolis, MN 

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

  1. De Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. New England Journal of Medicine 2011;364:1995-2005.
  2. Ryan CJ, Smith MR, De Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. New England Journal of Medicine 2013;368:138-48.