More CNS Adverse Events Associated With Enzalutamide Than Abiraterone/Prednisone Combo

Patients with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with enzalutamide (Xtandi) were more likely to experience central nervous system (CNS) events or fatigue than patients treated with the combination of abiraterone acetate (Zytiga) and prednisone. Further, patients treated with enzalutamide were more likely to reduce their treatment dose, according to results of a poster presented at the 2016 ASCO Annual Meeting.¹

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, and were eligible for at least six months prior to the index date and had ≥1 prostate cancer diagnosis.

Concerns regarding adverse events such as CNS conditions, fatigue, and pain potentially leading to dose reductions or treatment interruption are rising, according to the researchers.

“An earlier project produced data at ASCO GU and the International Prostate Cancer Update²that looked at both of these issues separately, while this new project brings both of them together,” said Ajay Behl, PhD, 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.

Abiraterone acetate is an antigen biosynthesis inhibitor, while enzalutamide is an androgen receptor inhibitor. But 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 abiraterone acetate, compared with 807 who had been prescribed enzalutamide. The population data were re-weighted to account for “the inverse probability of treatment weighting. After re-weighting, 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 (80% or less or 85% or less), according to the researchers.

Differences in CNS events in the first 3 months lacked statistical significance, but at 12 months, the differences were statistically significant: 37.5% of those men taking enzalutamide experienced a CNS event, compared with 30.3% of men taking abiraterone acetate (P= .017), according to the investigators.

Regarding fatigue, 28.6% of those on enzalutamide were impacted at 12 months, compared with 25% of those on abiraterone acetate (P= .033; HR 1.02).

Within 12 months, 24.4% of those on enzalutamide had a dose reduction to 85% or less of target dose, compared to 19.4% of those on abiraterone acetate (P= .022). Further, of those on enzalutamide, 20% had an even more drastic dose reduction to 80% or less of the target dose, compared with 13.6% of those on abiraterone acetate (P= .006).

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

Pilon D, Behl AS, Gozalo L, et al. Assessment of central nervous system (CNS) and dose reduction events in patients treated with abiraterone acetate plus prednisone (AA+P) or enzalutamide (ENZ). Presented at: 2016 ASCO Annual Meeting.J Clin Oncol.34, 2016 (suppl; abstr 5078).

Behl A, Ellis L, Pilon D, et al. Gaps in treatment amongst metastatic castration resistant prostate cancer (mCRPC) patients taking abiraterone acetate or enzalutamide.J Clin Oncol.34, 2016 (suppl 2S; abstr 334).