RWE Demonstrates Robust PSA Response and Treatment Adherence of Apalutamide in CRPC

Benjamin H. Lowentritt, MD, FACS

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) demonstrated high adherence rates and favorable prostate-specific antigen (PSA) response to apalutamide (Erleada) according to real-world evidence (RWE) presented at the 2021 American Urological Association Annual Meeting.¹

The analysis included data for 193 patients from routine urologic practice; investigators stratified results by Black vs non-Black patients. PSA response was defined as a minimum of 50% decline from baseline PSA; adherence was assessed using the medication possession ratio, defined as the number of days of supply within the entire exposure to therapy.

PSA response in the first 6 months after initiating apalutamide was observed in 83.5%, 86.5%, and 84.1% of patients in the overall (n = 176), Black (n = 29), and non-Black cohorts (n = 126), respectively, who had both pre- and post-index PSA measurements. At the 12 months, PSA response was reported in 86%, 93.1%, and 85.9% of patients in the overall (n = 178), Black (n = 29), and non-Black cohorts (n = 128), respectively.

Adherences rates were 93.6%, 90.1%, and 94.5% for patients in the overall (n = 193), Black (n = 33), and non-Black cohorts (n = 138), respectively.¹

“Apalutamide, a next-generation androgen receptor inhibitor, in conjunction with androgen deprivation therapy was approved by the [FDA] for [patients with] nmCRPC based on the results of randomized SPARTAN clinical study [NCT01946204],” said Benjamin H. Lowentritt, MD, FACS, director of Minimally Invasive Surgery and Robotics, and director of the Prostate Cancer Care Program at Chesapeake Urology in Towson, Maryland. “However, the effectiveness [of the agent] in real-world practice needs further evaluation.”

In the SPARTAN study, patients treated with apalutamide (n = 806) had a median metastasis-free survival of 40.5 months vs 16.2 months for those who received placebo (n = 401; HR, 0.28; 95% CI, 0.23-0.35; P < .001), meeting the primary end point of the study and leading the FDA approval.2 PSA response was an exploratory end point of the study.²

Investigators reported that 89.7% of patients treated with apalutamide had a PSA response.2 “Our real-world study showed that PSA response to apalutamide and continuous androgen deprivation therapy was robust and consistent with that in the SPARTAN study,” Lowentritt said.

To conduct the analysis, investigators used electronic medical records collected as part of routine clinical care from 95 US-based urology practices with dispensaries. PSA response and treatment patterns were evaluated from the index date—the first apalutamide dispensation among patients with non-metastatic CRPC—to the end of data availability (October 4, 2019), switch to another first- or second-generation antiandrogen, or death.

Baseline characteristics were evaluated in 12 months preceding the index date.

In this retrospective longitudinal cohort design, 193 patients with non-metastatic CRPC were treated with apalutamide; 33 (17%) were Black, 138 (72%) were non-Black, and 22 (11%) had an unknown racial background. Among the 3 cohorts, most patients (76%) were aged 71 to 90 years.

Evaluated patients had 2 apalutamide prescription fills and 12 months of prior prostate cancer management at baseline.

The mean baseline PSA levels for the overall (n = 190), Black (n = 33), and non-Black groups (n = 135) were 7 ng/mL, 10.5 nh/mL, and 5.6 ng/mL, respectively. PSA doubling times were reported for 90 (46.6%), 16 (48.5%), and 70 patients (50.7%), respectively, and the mean doubling times were 10.8, 10.2, and 10.1 months. The mean baseline testosterone for the overall (n = 146), Black (n = 22), and non-Black patient cohorts (n = 105) was 16.3 ng/dL, 15.1 ng/dL, and 17.3 ng/dL, respectively.

An additional efficacy end point was persistence rate, assessed as the proportion of patients who did not have a specific gap in treatment within a fixed period following the index date. At 6 months, 79.7%, 81.5%, and 80.6% of patients in the overall (n = 153), Black (n = 27), and non-Black cohorts (n = 108), respectively, did not have a gap in treatment over 45 days. Similarly, an over 90-day gap in treatment was not observed in 88.9%, 92.6%, and 87% of patients in the overall, Black, and non-Black groups, respectively.

A numerically higher proportion of Black patients were persistent at 12 months; specifically, 62.7%, 78.9%, and 58.6% of patients did not have an over 45-day gap in treatment in the overall (n = 102), Black (n = 19), and non-Black groups (n = 70), respectively. Correspondingly, an over 90-day gap in treatment was not observed in 69.6%, 78.9%, and 65.7% of patients in the overall, Black, and non-Black groups, respectively.

Lowentritt noted that although Black patients have higher incidence of prostate cancer, they comprised only 6% of the SPARTAN trial population.

“[This study provided] important information on real-word PSA responses in Black men, a population that is typically not well represented,” he concluded.

References

1. Lowentritt B, Brown G, Kernen K, et al. Real-world effectiveness and treatment adherence of apalutamide in non-metastatic castration-resistance prostate cancer patients. J Urol. 2021;206(suppl 1):e58. doi:10.1097/JU.0000000000001969.08
2. Smith MR, Saad F, Chowdhury F, et al; Spartan Investigators. N Engl J Med. 2018;378(15):1408-1418. doi:10.1056/NEJMoa1715546