In Prostate Cancer, Xtandi Sparks More Fatigue and Pain Than Zytiga

Patients with metastatic castration-resistant prostate cancer (mCRPC) who were treated with Xtandi (enzalutamide) were more likely to experience central nervous system (CNS) events or fatigue than patients treated with the combination of Zytiga (abiraterone acetate) and prednisone. Further, patients treated with Xtandi were more likely to reduce their treatment dose, according to results of a study presented in a poster session at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO), a gathering of 30,000 oncology professionals in Chicago.

Researchers conducted a retrospective analysis of records contained in the Marketscan insurance claims database, identifying patients who were initially treated with either therapy after October 2012, were eligible for at least six months prior to the index date and had one or more prostate cancer diagnosis.

Concerns are rising regarding side effects such as fatigue and pain that arise from disturbances to the CNS — which is composed of the brain, spinal cord and the nerves that send messages to and from them — because these can potentially lead to dose reductions or treatment interruption, according to the researchers.

“An earlier project produced data at ASCO GU and the International Prostate Cancer Update that looked at both of these issues separately, while this new project brings both of them together,” said Ajay Behl, associate director at Janssen Scientific Affairs in Horsham, Pennsylvania, who presented the poster. “The method of inclusion is the same, but the analytical platform is now unified,” added Behl in an exclusive interview.

Zytiga is an antigen biosynthesis inhibitor, while Xtandi is an androgen receptor inhibitor. Both are indicated for the treatment of mCRPC. Although there have been no randomized head-to-head studies of the comparative effectiveness of the two drugs, a 2014 study that conducted an “indirect comparison” of the therapies in patients previously treated with docetaxel found that each sparked about an equal boost in overall survival, but that Xtandi may have been more effective in controlling prostate-specific antigen, which at rising levels is considered a potential marker for progressive disease.

However, both drugs come with side effects. “Fatigue and pain are the two most important issues coming up in all the different analyses, and providers do notice them in patients,” explained Behl. “Providers and physicians need to see how CNS issues could affect dosage reductions, and determine which drug provides the most benefit.”

The researchers identified 2,196 patients who had been prescribed Zytiga, compared with 807 who had been prescribed Xtandi. The population data were re-weighted according to a statistical formula, after which the groups contained approximately 1,500 patients each, Behl explained. The two treatment groups were then compared for CNS events such as fatigue and pain and relative dose intensity, according to the researchers.

Differences in CNS events in the first three months lacked statistical significance, but at 12 months, the differences were statistically significant: 37.5 percent of those men taking Xtandi experienced a CNS event, compared with 30.3 percent of men taking Zytiga, according to the investigators.

Regarding fatigue, 28.6 percent of those on Xtandi were impacted at 12 months, compared with 25 percent of those on Zytiga.

Within 12 months, 24.4 percent of those on Xtandi had a dose reduction to 85 percent or less of target dose, compared to 19.4 percent of those on Zytiga. Further, of those on Xtandi, 20 percent had an even more drastic dose reduction to 80 percent or less of the target dose, compared with 13.6 percent of those on Zytiga.

However, the difference as far as pain was not statistically significant, even at 12 months. In the Xtandi group, 15.3 percent of patients experienced a pain event, compared with 12.9 percent of those who received Zytiga.