Better Treatment Needed for Androgen Receptor Adverse Events


While the majority of patients on androgen receptor therapy experienced adverse events, more than a third did not have them resolved.

While second-generation androgen receptors such as apalutamide (Erleada) and enzalutamide (Xtandi) have improved outcomes for men with nonmetastatic castrate-resistant prostate cancer (nmCRPC), they can come with adverse events (AEs) that are often unresolved, according to recent research presented at the 2021 Genitourinary Cancers Symposium.

“The objective of the present study was to describe the patient characteristics, the frequency of a disease or adverse events amongst patients receiving apalutamide or enzalutamide [and] how these adverse events are managed in a real-world setting, and what is the health care resource utilization for these patients,” said study author Arif Hussain, MD, professor of medicine at the University of Maryland Medical System.

The researchers analyzed 368 patients with nmCRPC who were taking apalutamide and 333 on enzalutamide. In this group, 72% and 78.8% experienced 1 or more AE in the apalutamide and enzalutamide group, respectively. Hussain noted that they did not investigate outcomes for darolutamide (Nubeqa) because they did not have sufficient data on the drug at the time of the study.

The most common AEs in the apalutamide and enzalutamide groups were:

  • Fatigue/asthenia (30.2% vs 38.7%, respectively)
  • Hot flush (14.1% vs 13.5%)
  • Arthralgia (14.4% vs 12.9%)

Notably, cognitive and mental changes were also observed in 5.4% of men on apalutamide and 7.8% of men on enzalutamide.

From the total group, the researchers further analyzed 125 patients on apalutamide and 125 patients on enzalutamide who experienced 1 or more AE for a more in-depth evaluation. Nearly three-fourths of this group was Caucasian; 84% and 88% had an ECOG score between 0-1; and the median prostate-specific antigen (PSA) score was 13 ng/ml and 11 ng/ml for apalutamide and enzalutamide, respectively.

Many patients on apalutamide and enzalutamide (43.6% vs. 39.4%, respectively) did not have their AEs resolved. For those who did have toxicities resolved, it took an average of 60 and 56 days for the apalutamide and enzalutamide groups, respectively.

The most common approaches for AE management in the apalutamide and enzalutamide arms were:

  • Treatment for the AE (36.8% vs. 39.2%, respectively)
  • Drug discontinuation (8% vs. 12.8%)
  • Dose reduction (7.2% vs. 8.0%)
  • Hospitalization (5.6% vs. 4.0%)

The researchers ultimately concluded that there is a resource use burden to manage AEs for these agents, and patients and providers should discuss toxicities before deciding on a treatment regimen.

“The results demonstrate the importance of safety and tolerability, which should be key considerations and shared clinician-patient decision-making regarding androgen receptor inhibitor targeted therapy in nmCRPC patients,” Hussain said.


Jiang S, Varghese D, Appukkuttan S, et. al. Frequency, management, and resource use of adverse events (AEs) in nonmetastatic castrate-resistant prostate cancer (nmCRPC) patients receiving apalutamide or enzalutamide: A real-world study. Presented at: 2021 Genitourinary Cancers Symposium. Feb. 11-13. Virtual. Abstract 217.

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