Comparison of prostate-specific antigen (PSA) response in patients with de novo metastatic castration-sensitive prostate cancer (mCSPC) treated with apalutamide (APA) vs abiraterone acetate (ABI): A real-world (RW) causal analysis.

e17070 Background: Patients with de novo mCSPC experience poor clinical outcomes which can be improved by treatment with androgen receptor signaling inhibitors (ARSIs). A prior RW study of patients with mCSPC initiated on APA or ABI found that APA initiators had significantly higher rates of PSA decline ≥90% (PSA90). This study compared PSA90 response by 6-months for patients with de novo mCSPC initiated on APA or ABI. Methods: Claims from the Komodo Health Solutions Research Database were linked with electronic medical records in US community urology practices from PPS Analytics. Exclusive APA and ABI cohorts were defined based on an initial pharmacy claim or dispensation for APA or ABI on or after 9/17/2019 (index date). Castration-sensitive patients were defined as de novo mCSPC if metastasis was observed ≤180 days after the initial prostate cancer (PC) diagnosis. Patients were also included if they had ≥12 months of pre-index clinical activity and had ≥1 PSA test within 13 weeks pre-index. Patients were followed until the earliest of index ARSI discontinuation (i.e., gap ≥90 days supply) or switch, radiopharmaceutical use, or end of clinical activity or data availability (9/30/2022). Inverse probability treatment weighting (IPTW) was used to balance pre-index covariates between cohorts (i.e., age, race, region, payer type, index year, time from metastasis to index date, time from first PC diagnosis to index date, metastasis location, use of androgen deprivation therapy, first-generation antiandrogens or chemotherapy, most recent PSA and testosterone levels, and earliest Gleason score). PSA90 was defined as the earliest ≥90% decline in PSA relative to the most recent value within 13 weeks pre-index. The proportion of patients achieving PSA90 by 6-months was compared using a weighted Kaplan-Meier analysis and the time-to-PSA90 response was compared using a weighted Cox proportional hazards model. Results: A total of 356 APA and 324 ABI patients with de novo mCSPC were identified. Patient characteristics were balanced with IPTW (Table). By 6 months post-index, 82.0% of APA patients and 73.5% of ABI patients had a PSA measurement. By 6 months, significantly more APA patients attained PSA90 response relative to ABI patients (62.2% vs 41.6%; p<0.001; Table). Median time-to-PSA90 was 3.6 months for APA, and 10.3 months for ABI. Conclusions: This US-based RW study showed that a higher proportion of patients with de novo mCSPC initiated on APA achieved a deep, early PSA response relative to those on ABI. Table: see text