Apalutamide Demonstrates Robust Real-World Effectiveness in mCSPC

Benjamin Lowentritt, MD, FACS

Patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with the androgen receptor–signaling inhibitor (ARSI) apalutamide (Erleada) achieved prostate-specific antigen (PSA) responses that trended higher and rates of progression to castration resistance that trended lower than those receiving enzalutamide (Xtandi) or abiraterone acetate (Zytiga), according to data from a retrospective study presented at the 2023 AUA Annual Meeting.

The median follow-up for PSA outcomes was 203 days, 178 days, and 205 days for apalutamide, enzalutamide, and abiraterone acetate, respectively. In these groups, rates of PSA90 response were 48.0%, 35.1%, and 36.7%, respectively, at 3 months; 67.4%, 52.6%, and 46.7%, respectively, at 6 months; and 72.3%, 61.6%, and 54.7%, respectively, at 12 months. The median time to PSA90 was 3.2 months, 5.2 months, and 7.6 months, respectively.

Additionally, rates of PSA0.2 responses at 3 months were 43.3%, 32.4%, and 34.0%, respectively, and the 6-month rates were 67.1%, 56.6%, and 48.0%, 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 apalutamide group, 4.4 months in the enzalutamide cohort, and 7.1 months in the abiraterone acetate group.

The median follow-up to evaluate progression to castration resistance and castration resistance–free survival (CRFS) was 341 days for apalutamide (n = 589), 330 days for enzalutamide (n = 597), and 520 days for abiraterone acetate (n = 553). Progression to castration resistance rates at 6 months were 6.5%, 10.3%, and 16.4%, respectively, and 20.9%, 22.4%, and 31.0%, 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.

Additionally, the CRFS rates for the apalutamide, enzalutamide, and abiraterone acetate cohorts, respectively, were 91.5%, 87.5%, and 81.6% at 6 months; 76.2%, 74.1%, and 65.1% at 12 months; 66.4%, 62.8%, and 56.1% at 18 months; and 62.0%, 55.1%, and 50.5% at 12 months.

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

The retrospective, longitudinal cohort study utilized clinical data from the Precision Point Specialty Analytics that was collected as part of routine care from 95 community-based urology clinics throughout the United States.

The study period ranged from February 1, 2017, to April 1, 2022, and patients were included if they were male, 18 years or older on the index date, and received 1 or more in-office dispensations for apalutamide, enzalutamide, or abiraterone acetate. 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.

If they had evidence of CR before, or on, the index date; previously received an ARSI prior to the index date or received 2 or more ARSIs on the index date; or had prior radiopharmaceuticals, they were excluded. Moreover, they could not have an index date that occurred prior to the FDA approval of each specific agent.

Notably, concurrent use of androgen receptor therapy was not required to be included in any of the ARSI cohorts, nor was concurrent use of prednisone needed to be included in the abiraterone acetate cohort.

The key objective of the study was to describe the real-world PSA outcomes and disease progression among patients with mCSPC who began treatment with apalutamide, enzalutamide, or abiraterone acetate in US urology practices.

To report PSA responses, investigators utilized the most recent baseline PSA value in those with at least 1 PSA measurement in the 13 weeks before, or on, the index date. To evaluate rates of PSA90, PSA0.2, progression to castration resistance, and CRFS, investigators leveraged Kaplan Meier analyses; this was done separately for each ARSI cohort.

PSA90 was defined as experiencing a reduction in PSA of at least 90% from the most recent baseline PSA value, and PSA0.2 was 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. Moreover, 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.

PSA outcomes were censored at the earliest of index treatment discontinuation, radiopharmaceutical use, end of clinical activity, or end of availability of data. Progression to castration resistance and CRFS were censored at the earliest of end of clinical activity or end of availability of data.

Notably, all analyses were descriptive and were not adjusted for potential baseline confounders, according to the study authors.

Of the 1739 patients identified for the study, 589 were in the apalutamide cohort, 597 patients were in the enzalutamide cohort, and 553 patients were in the abiraterone acetate cohort. 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 apalutamide, enzalutamide, and abiraterone acetate cohorts was 1.5 months, 2.4 months, and 1.8 months, respectively. Most patients in the apalutamide (96.3%), enzalutamide (94.5%), and abiraterone acetate (95.7%) cohorts concurrently received ADT. In the abiraterone acetate cohort, 94.6% of patients were receiving concurrent use of prednisone vs 2.0% and 1.3% of those in the apalutamide and enzalutamide cohorts, respectively.

Prior ADT was received by 90.5%, 89.8%, and 90.8% of patients in the apalutamide, enzalutamide, and abiraterone acetate cohorts, respectively; 11.4%, 15.7%, and 15.7% of patients, respectively, previously received a first-generation ARI. Additionally, across the cohorts, 28.3% of patients received bone antiresorptive therapy.

The majority of patients had a PSA test at baseline within 13 weeks before or on the start of treatment with apalutamide (81.2%), enzalutamide (76.0%), and abiraterone acetate (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 apalutamide, enzalutamide, and abiraterone cohorts, respectively, had one or more on-treatment PSA tests, with almost all tests occurring within the 6 months following treatment initiation. The median number of follow-up PSA tests per year was 3.8, 3.3, and 5.5, respectively.

As the enzalutamide cohort had fewer patients with at least 1 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 apalutamide, enzalutamide, and abiraterone acetate 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 apalutamide 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 abiraterone acetate 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 enzalutamide cohort had a lower proportion of patients with at least 1 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 3 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.

Reference

Lowentritt B, Du S, Rossi C, et al. Prostate-specific antigen response and time-to-castration resistance among patients with metastatic castration sensitive prostate cancer initiated on apalutamide, enzalutamide, or abiraterone acetate. J Urol. 2023;209(4):e387. doi:10.1097/JU.0000000000003257.14