Erleada Has ‘Robust Real-World Effectiveness’ in Prostate Cancer

Patients with metastatic castration-sensitive prostate cancer (mCSPC) receiving Erleada (apalutamide) tended to have a higher rate of prostate-specific antigen (PSA) respnses and lower rates of of progression to castration resistance — prostate cancer that continues to grow, even with low amounts of testosterone in the body — than those receiving Xtandi (enzalutamide) or Zytiga (abiraterone acetate), according to data from a retrospective study presented at the 2023 AUA Annual Meeting.

PSA and Disease Outcomes

The median follow-up for PSA outcomes was 203 days, 178 days and 205 days for Erleada, Xtandi and Zytiga, respectively. In these groups, rates of PSA90 response, which is defined as a 90% or more decrease in PSA levels, were 48%, 35.1% and 36.7%, respectively, at three months; 67.4%, 52.6% and 46.7%, respectively, at six months; and 72.3%, 61.6% and 54.7%, respectively, at 12 months.

The median time to a 90%or more decrease in PSA was 3.2 months, 5.2 months and 7.6 months, respectively.

Additionally, rates of PSA0.2 responses, which are defined as having a PSA value of 0.2 ng/mL or less among patients with a recent baseline PSA of greater than 0.2 ng/mL, at three months were 43.3%, 32.4% and 34%, respectively, and the six-month rates were 67.1%, 56.6% and 48%, respectively. The 12-month rates were 80.6%, 63.2% and 58.4%, respectively. The median time to PSA0.2 was 3.5 months in the Erleada group, 4.4 months in the Xtandi group and 7.1 months in the Zytiga group.

The median follow-up to evaluate progression to castration resistance and castration resistance–free survival (CRFS) was 341 days for Erleada (589 patients), 330 days for Xtandi (597 patients) and 520 days for Zytiga (553 patients). Progression to castration resistance rates at six months were 6.5%, 10.3% and 16.4%, respectively, and 20.9%, 22.4% and 31%, respectively, at 12 months. At 18 months, these rates were 29.3%, 32.4% and 40.3%, respectively, and at 24 months, these rates were 33.5%, 38.6% and 44.5%, respectively.

Real-world study results showed that Erleada was promising in certain patients with prostate cancer.

Additionally, the CRFS rates for the Erleada, Xtandi and Zytiga cohorts, respectively, were 91.5%, 87.5% and 81.6% at six months; 76.2%, 74.1% and 65.1% at 12 months; 66.4%, 62.8% and 56.1% at 18 months; and 62%, 55.1% and 50.5% at 12 months.

“In this real-world study of patients with mCSPC treated in a community-based urology setting, Erleada demonstrated robust real-world effectiveness with respect to PSA response and progression to castration resistance, consistent with results from prior real-world studies,” Dr. Benjamin Lowentritt of Chesapeake Urology, and colleagues, wrote in the poster.

Study Details

The study period ranged from Feb. 1, 2017, to April 1, 2022, and patients were included if they were male, 18 years or older on the index date and received one or more in-office dispensations for Erleada, Xtandi or Zytiga. Patients must have had 12 or more months of clinical activity prior to the index date. Moreover, evidence of metastatic disease defined by presence of bone, nodal or visceral metastasis must have been present prior to, or on, the index date.

The main goal of the study was to describe the real-world PSA outcomes and disease progression among patients with mCSPC who began treatment with Erleada, Xtandi or Zytiga in United States. urology practices.

Time from the index date to patients’ date of castration resistance as identified in the clinical data represented progression to castration resistance. Time from the index date to the earliest of the patients’ date of castration resistance or death represented CRFS.

Of the 1,739 patients identified for the study, 589 were in the Erleada group, 597 patients were in the Xtandi group and 553 patients were in the Zytigag group. The approximate mean age of all patients was 75.9 years, and most patients were White (71.3%).

The median time between metastasis and start of index treatment for the Erleada, Xtandi and Zytiga cohorts was 1.5 months, 2.4 months and 1.8 months, respectively. Most patients in the Erleada (96.3%), Xtandi (94.5%) and Zytiga (95.7%) groups concurrently received androgen deprivation therapy. In the Zytiga group, 94.6% of patients were receiving concurrent use of prednisone (a steroid), compared with 2% and 1.3% of those in the Erleada and Xtandi groups, respectively.

Prior androgen deprivation therapy was received by 90.5%, 89.8% and 90.8% of patients in the Erleada, Xtandi and Zytiga groups, respectively; 11.4%, 15.7% and 15.7% of patients, respectively, previously received a first-generation androgen rectptor inhibitors. Additionally, across the cohorts, 28.3% of patients received bone antiresorptive therapy, which is used to increase bone strength.

The majority of patients had a PSA test at baseline within 13 weeks before or on the start of treatment with Erleada (81.2%), Xtandi (76%) and Zytiga (80.7%). The mean PSA levels at baseline in these cohorts were 19.2 ng/mL, 18.8 ng/mL and 24.3 ng/mL, respectively. Moreover, in those with available data, the mean PSA doubling times were 9.5 months, 7.9 months and 4.8 months, respectively.

Overall, 80.8%, 71.2% and 83.5% of patients in the Erleada, Xtandi and Zytiga groups, respectively, had one or more on-treatment PSA tests, with almost all tests occurring within the six months following treatment initiation. The median number of follow-up PSA tests per year was 3.8, 3.3 and 5.5, respectively.

Potential Study Limitations

As the Xtandi cohort had fewer patients with at least one PSA follow-up test than the other cohorts, investigators noted this may have impacted the results. Additionally, the median follow-up for PSA outcomes were 203 days, 178 days and 205 days in the Erleada, Xtandi and Zytiga cohorts.

“(These are) retrospective data; it’s a real-world evidence dataset, which has its inherent limitations,” Lowentritt said in a presentation of the data, “but this did show at least a robust response in the Erleada arm. Certainly, further studies will be needed to potentially pull away some of the baseline characteristics (needed) to understand any further differences.”

Limitations of the study included that the database used is representative of community urology and may not be representative of the entire population of patients with this disease in the United States; as such, this may not allow for the generalizability of the study in certain settings. Additionally, the study did not take use of prednisone in combination with Zytiga into account, as it is FDA approved for mCSPC.

Moreover, the study also included those who received treatment through in-office medication dispensation, which may not represent those who receive external dispensation of those in urology practices that do not provide in-office dispensation.

Further, the authors noted that the clinical data used may have inaccuracies or omissions and does not include diagnoses, medical services or prescriptions filled outside of the network of urology practices.

“The Xtandi cohort had a lower proportion of patients with at least one follow-up PSA test which could impact the results,” the authors wrote.

Notably, analyses were descriptive with no adjustment made for observable cofounders between the three cohorts. Additional studies will be needed to adjust for these cofounders to draw comparative conclusions, the study authors underscored.

“While ARSIs with higher proportions achieving PSA90 were observed to have lower rates of progression to castration resistance, further studies are needed to understand this relationship,” the authors conluded.

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