AUA 2018: Association of Dose Reduction of Abiraterone Acetate plus Prednisone or Enzalutamide and PSA Progression in Veterans with mCRPC

San Francisco, CA ( Abiraterone acetate and enzalutamide are oral agents which have both been shown to reduce PSA, delay time to PSA progression, and prolong overall survival in men with metastatic castrate-resistant prostate adenocarcinoma (mCRPC).  Stephen Freedland, MD,  from Cedars-Sinai Medical Center, presented his group’s data evaluating the association between the dose reduction of these agents, which can sometimes be necessary in order to minimize side-effects or toxicities, and PSA progression in men with mCRPC. 

Using a Veterans Health Administration database, they captured retrospective data of men with mCRPC who received >1 prescription for either abiraterone or enzalutamide, regardless of prior chemotherapy. After selecting their samples based on criteria such as >12 months of prior PSA observations prior to the prescription, and >2 PSA measurements within the 3 months post-prescription, they identified 6,069 men. The primary outcome of the study was time to PSA progression, which was defined as the first rise in PSA of at least 2ng/mL and at least 25% above that patient’s nadir PSA value. 

During follow-up, PSA progression occurred in 62.7% of patients. The group used a Cox proportional hazard regression model to evaluate the association between PSA progression and a relative dose intensity (RDI) of the two oral agents. During follow-up at least one RDI <80% was noted in 64.4% of patients. The model showed then when an RDI of <80% was present when both of the oral agents were grouped together, this was associated with an 8.8% higher likelihood of having PSA progression. In subgroup analysis, only patients on enzalutamide had a statistically significant increase in PSA progression. They concluded that there is a high proportion of patients who have a dose reduction of oral oncolytics and that dose reduction of enzalutamide is associated with a statistically significant increased risk of PSA progression in such patients. 

Presented by: Stephen Freedland MD, Cedars-Sinai Medical Center, Los Angeles, CA
Co-Authors: Yinong Young-Xu, White River Junction, VT, Sophia Li, Horsham, PA, Dominic Pilon, Montréal, Canada, Rachel Bhak, Sahil Narkhede, Boston, MA, Rhiannon Kamstra, Montréal, Canada, Ajay Behl, Horsham, PA, Patrick Lefebvre, Montréal, Canada, Alexander Fuld, Hanover, NH

Written by: Brian Kadow, MD. Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia PA at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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