Real-world comparison of prostate-specific antigen (PSA) response in metastatic castration-sensitive prostate cancer (mCSPC) patients treated with apalutamide (APA) without docetaxel vs darolutamide (DARO) without docetaxel.

Abstract

106 Background: APA and DARO are androgen receptor pathway inhibitors (ARPIs) approved for the treatment of mCSPC in combination with androgen deprivation therapy (ADT), with DARO also approved in combination with ADT and docetaxel. Deep PSA response, evaluated as ≥90% decline in PSA (PSA90), is an important indicator of treatment prognosis after ARPI initiation, with rapid response associated with longer survival. This study compared PSA90 response in a sample of ARPI-naïve patients with mCSPC initiated on APA without docetaxel versus DARO without docetaxel. Methods: Linked US healthcare databases (PPS Analytics and Komodo Research Database; 1/1/2016-4/30/2025) were used in this longitudinal, retrospective cohort analysis. Patients with mCSPC were grouped into two cohorts based on the first APA or DARO dispensation or pharmacy claim on or after 8/5/2022 (index date) and followed until the earliest of index ARPI discontinuation or switch, docetaxel or radiopharmaceutical initiation, end of clinical activity or end of data availability (4/30/2025). PSA90 was defined as the earliest ≥90% decline in PSA relative to the most recent detectable pre-index PSA. Baseline patient characteristics were balanced between cohorts using inverse-probability of treatment weighting. Weighted Kaplan-Meier and Cox proportional hazards models were used to compare time-to-PSA90 and proportion achieving PSA90 response between APA vs DARO. Results: Baseline characteristics were well balanced between APA (N=714) and DARO (N=145) cohorts after weighting (Table). Mild-to-moderate diabetes (APA: 34.6%, DARO: 40.7%) and peripheral vascular disease (APA: 33.4%, DARO: 33.2%) were the most common comorbidities. Most patients had bone (APA: 52.2%, DARO: 50.5%) or nodal metastasis (APA: 51.0%, DARO: 49.2%). By 6 months, APA patients had a statistically significant 49% increase in PSA90 response rates as compared to DARO (hazard ratio [HR]: 1.49 [95% CI: 1.07, 2.07]; p=0.017; Table). Median time-to-PSA90 response was 2.8 months for APA and 3.3 months for DARO. Conclusions: This real-world study of patients with mCSPC demonstrated a significant increase in the likelihood of achieving deep PSA response for patients initiated on APA without docetaxel relative to those treated with DARO without docetaxel. Even without treatment intensification with docetaxel, APA remains an effective treatment option for achieving early deep PSA response. Weighted cohorts. Baseline APAN=714 DARON=145 Standardized difference (%) Median age, years 75 74 4.9 White / Black (%) 59.6 / 21.2 58.8 / 21.6 1.7 / 0.9 PSA level (%), ng/mL  >0.2 to ≤2 34.1 31.7 5.1  >2 to ≤10 32.5 35.2 5.8  >10 to <20 9.8 9.6 0.7  ≥20 23.6 23.5 0.4 Follow-up PSA90 response (%) HR (95% CI),p-value By 6 months 74.6 56.1 1.49 (1.07, 2.07), 0.017