ASCO 2019: Abiraterone Acetate plus Prednisone without Continuing LHRH-Therapy in Patients with Metastatic Chemotherapy: Naive Castrations-Resistant Prostate Cancer — Results from the SPARE-Trial

Chicago, IL (UroToday.com) Cougar 301 and Cougar 302 established the role of abiraterone in patients with 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).1 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).2  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 study evaluates abiraterone acetate plus prednisone (AA+P) without continuing LHRH-therapy in patients with chemotherapy naïve mCRPC.
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This abstract provides data on 67 patients who were randomly assigned to either ADT+Abiraterone (Arm A) or Abiraterone alone (Arm B). Both groups received prednisone as is standard of care with abiraterone. The primary endpoint of this study was radiographic progression-free survival (rPFS) at 1 year. At the time of this abstract, there were 34 patients in Arm A and 33 patients in Arm B. The median prostate-specific antigen (PSA) was 31.9 in Arm A and 20.59 in Arm B. Of note, one patient in Arm A did not have castrate levels of testosterone at the beginning of the study. All patients in Arm B started with castrate levels of testosterone (<50 ng/dL).

In terms of the primary endpoint, the rPFS was 90% in Arm A and 78% in Arm B. This is a small study but these values compare favorably to the patients in COUGAR 302, where the rPFS at 1 year was around 60%. The time to PSA progression was 9.6 months in Arm A and 11.2 months in Arm B – these are similar to COUGAR 302, where the median time to PSA progression was 11.1 months. Neither the time to PSA progression or rate of rPFS at 1 year was significantly different between the two arms. Of note, 6 patients in Arm B had testosterone levels arise above castrate levels within 28 days of discontinuation of abiraterone/prednisone.
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This study provides initial data on mCRPC patients undergoing therapy with abiraterone/prednisone and suggests that the efficacy may not be compromised if LHRH therapy is discontinued. It would be interesting to evaluate the quality of life metrics in addition to the cost-effectiveness analysis of this approach. Additional follow up and larger studies are necessary to fully evaluate this unique strategy. 

Presented by: Carsten Henning Ohlmann, MD, Malteser Hospital Bonn, Bonn, Germany

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

References:
  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.
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