|The following article features coverage from the American Urological Association (AUA) 2021 annual meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
The burden of treatment discontinuation from adverse events in real-world use is 32% higher for apalutamide and 49% higher for enzalutamide than reported in clinical trials of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), according to data presented at the American Urological Association (AUA) 2021 Virtual Experience.
The retrospective, observational study included patients diagnosed with nmCRPC from the Precision Point Specialty (PPS) Analytics Portal for Prostate Cancer database who initiated apalutamide or enzalutamide use as an initial androgen receptor antagonist (ARA) from February 1, 2018, to September 30, 2020. Eligible participants were adult males aged 18 years or older with no history of other primary cancer other than skin cancer. The study authors used survival analyses to assess time to discontinuation and performed a supplemental chart review to identify reasons for dose reduction and discontinuation.
A total of 2636 patients were included — 1023 (39%) who used apalutamide and 1613 (61%) who used enzalutamide. Participants’ mean age at ARA initiation was 77.8 years, 68% were White, and 73% had a Charlson Comorbidity Index (CCI) score of zero. Those who used apalutamide and enzalutamide, respectively, had a median prostate-specific antigen of 3.7 ng/dL and 4.1 ng/dL, a median follow-up duration of 18.7 and 12.1 months, and a median therapy duration of 12.9 and 9.8 months.
About 41% of patients discontinued use of their initial ARA, and 9.4% switched initial ARA therapy. The median time to discontinuation was 9.0 and 7.4 months, and the median time to switch therapies was 4.8 and 6.5 months among users of apalutamide and enzalutamide, respectively.
In the random subset of patients in the supplemental review (977 patients; 455 apalutamide users and 522 enzalutamide users), adverse events (AE) were the most frequently reported reason for drug discontinuation (43.4% for apalutamide and 58.2% for enzalutamide). For the 5.6% of patients who had a dose reduction, the most frequently reported reason was an AE in 72.4% of apalutamide patients and in 73.1% of enzalutamide patients.
The discontinuation rate from AEs was 28% higher (43% vs 15%, respectively) in apalutamide patients and 41% higher (58% vs 17%, respectively) in enzalutamide patients in the real world compared with the rate in clinical trials.
The investigators noted that all information obtained from the database was dependent on proper documentation of the electronic medical records. In addition, data were lacking for outcome analysis such as discontinuation rates for patients who used darolutamide, another second-generation ARA.
“The burden of treatment discontinuation due to adverse events within real-world utilization is markedly higher than reported in nmCRPC clinical trials,” stated the researchers. “Our results show the need for additional therapies with improved safety profiles and warrant future studies with all nmCRPC agents.”
Disclosure: This study was funded by Bayer Healthcare Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Appukkuttan S, Madaj K, Du Y, et al. Real-world utilization of apalutamide and enzalutamide in non-metastatic castrate resistant prostate cancer: a retrospective study. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. MP24-03.