SAN FRANCISCO – Statins do not reduce the effectiveness of abiraterone acetate in men with castration-resistant prostate cancer, and they may even prove to add to therapy, according to data reported at the Genitourinary Cancers Symposium.
In a retrospective cohort study of 224 patients treated with abiraterone, duration of abiraterone acetate therapy, used as a surrogate for time to disease progression, was 5 months longer for men taking statins.
Dr. Lauren C. Harshman
Prior work in patients with hormone-sensitive disease has suggested that statins compete with the androgen dehydroepiandrosterone sulfate – a precursor of more potent androgens – for cellular uptake via the SLCO2B1 transporter (JAMA Oncol. 2015 Jul;1:495-504). But “contrary to our initial hypothesis and the preclinical data that drove our initial hypothesis, there was a trend toward longer abiraterone duration in statin users,” commented Dr. Lauren C. Harshman of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, and Harvard Medical School, both in Boston. “(A statin) may be additive with abiraterone’s effect on androgen biosynthesis. Alternatively, statins could be inhibiting abiraterone’s uptake by the liver and might be prolonging the drug exposure,” she said at the 2016 Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology.
While the findings are “intriguing,” they are not yet ready for clinical application, according to Dr. Harshman, and “need to be validated before you would ever start a statin purely for prostate cancer treatment.”
Based on preclinical data, the researchers had hypothesized that statins would compete with abiraterone for cellular influx by SLCO2B1, thereby reducing abiraterone’s inhibition of androgen biosynthesis and its clinical efficacy.
They analyzed data from men treated for predominantly metastatic castration-resistant prostate cancer with abiraterone (Zytiga) at Dana-Farber between 2008 and 2015. In about three-fourths of cases, abiraterone was being given as the first treatment for castration-resistant disease. Overall, 41% of men were taking statins when they began abiraterone.
With a median follow-up of 27.8 months, the median duration of abiraterone therapy was 14.2 months for statin users and 9.2 months for nonusers, according to data reported in a poster session. In a multivariate analysis, statin use continued to predict a longer duration of abiraterone therapy, although the prolongation was not statistically significant.
Findings were much the same, with a trend toward greater benefit for statin users, among the subset of patients who had not previously received enzalutamide or docetaxel chemotherapy (21.3 vs. 14.8 months).
“We are working with another center to add numbers to see if we see a similar trend,” concluded Dr. Harshman, who disclosed that she receives research funding from Janssen, the maker of abiraterone (Zytiga). “We are thinking about how to test this prospectively, whether in a randomized trial or some sort of trial where you might add abiraterone plus statins.”
The investigators are also analyzing the impact of single-nucleotide polymorphisms in the SLCO transporter on abiraterone’s efficacy in patients with castration-resistant prostate cancer, she said.