Neal D. Shore, MD
Since 2010, several novel therapies have been approved for use in metastatic castration-resistant prostate cancer (mCRPC). Although they have expanded the therapeutic repertoire for clinicians, they also bring a new set of challenges for the optimal clinical management of patients with mCRPC. Data obtained from clinical trials are crucial in determining optimal efficacy and safety of therapies in a controlled setting. However, the trial setting may fail to provide an understanding of the challenges associated with novel therapies. Real-world data obtained from large retrospective studies can also deliver useful insights into the clinical challenges associated with these newer therapies, such as medication adherence and cognitive adverse events (AEs), which may not have been fully explored.
Medication Adherence With Oral Anti-Cancer Therapies
The number and availability of oral anti-cancer drugs has increased in recent years. While multiple studies have indicated that the majority of patients prefer oral therapy compared with intravenous therapy, this also shifts a large part of medication adherence responsibility from the clinician to the patient. The linkage between adherence rates and treatment efficacy may have a significant impact on patient outcomes; as such, medication adherence represents an increasing concern for the optimal therapeutic management of patients with mCRPC. Historically, determining adherence to anti-cancer therapies has been difficult to predict, with rates varying widely between 16% and 100%.1
In January 2016, Ajay Behl, PhD, and colleagues presented data on the treatment gaps in patients with mCRPC who were treated with abiraterone or enzalutamide at the 2016 Genitourinary Cancers Symposium.2
Abiraterone acetate, an inhibitor CYP17A1 that blocks extragonadal androgen biosynthesis, and enzalutamide, a direct antagonist of the androgen receptor (AR), are among the next-generation agents most recently approved for use in mCRPC. Both agents are available as oral therapies.
In the retrospective study, investigators utilized the Truven Health MarketScan Research Databases to analyze nearly 3400 patients with mCRPC who were initiated on either abiraterone or enzalutamide therapy. Patient discontinuation patterns were observed until loss to follow-up or data unavailability, and Kaplan-Meier survival curves compared the rates of having a refill gap (Table)
Compared with patients initiating with abiraterone therapy, patients initiating with enzalutamide had significantly higher rates of refill gaps of ≥30 days or ≥60 days after 6 months (≥30 days: 18.3% vs 11.7%; ≥60 days: 8.4% vs 5.2%), 9 months (≥30 days: 24.9% vs 16.9%; ≥60 days: 12.7% vs 7.9%), and 12 months (≥30 days: 30.1% vs 20.9%; ≥60 days: 15.9% vs 9.1%).2
Little additional data are available on the specific adherence rates of abiraterone or enzalutamide. In one US study of patients taking abiraterone acetate plus prednisone, the adherence rate, as measured by the medical possession ratio (MPR), was >90% after 6 months, 9 months, and 12 months.3
A Canadian study found that optimal adherence, as defined by an MPR of at least 80% at 6 months, was achieved by 83% of patients. Nearly 80% achieved an MPR of ≥90%. At 1 year, 82% of patients maintained optimal adherence.4
While these data support that nonadherence to abiraterone is relatively low, additional studies are needed to determine the reasons driving nonadherence with enzalutamide and potential contributing factors. To date, no other specific data exist that have examined the adherence rate of patients receiving enzalutamide. The reasons for oral anti-cancer therapy nonadherence are complex and involve several factors.