Survival benefit associated with first-line androgen receptor pathway inhibitors for de novo metastatic castration-sensitive prostate cancer.

BACKGROUND: Limited real-world data exist on the effectiveness of treatment intensification (TI) with androgen receptor pathway inhibitors (ARPI) in de novo metastatic castration-sensitive prostate cancer (mCSPC). This study compared outcomes of TI or first-generation nonsteroidal antiandrogens (NSAAs) to androgen-deprivation therapy (ADT) alone in US patients with de novo mCSPC. METHODS: Veterans Affairs patients with de novo mCSPC (February 2018-June 2020) confirmed via chart review were grouped into ADT alone, ADT + NSAAs, or ADT + ARPI cohorts using predefined recruitment quotas. Outcomes included inverse probability of treatment weighting (IPTW)-adjusted overall survival (OS), progression to metastatic castration-resistant prostate cancer (mCRPC), and prostate-specific antigen (PSA) response. RESULTS: A total of 384 patients were identified (ADT alone: 163, ADT + NSAA: 101, ADT + ARPI: 120). Median follow-up was 37.2, 38.1, and 34.8 months for ADT alone, ADT + NSAA, and ADT + ARPI, respectively. Compared with ADT alone, ADT + ARPI showed significantly better OS (HR [95% CI]: 0.61 [0.43 to 0.87], p = 0.007), lower risk of progression to mCRPC (0.46 [0.33 to 0.66], p < 0.001), and higher PSA response rate (PSA decline of ≥50% and ≥90% from baseline, and to <0.2 ng/mL and <0.1 ng/mL any time during first-line treatment; all p < 0.05). Outcomes with ADT + NSAA did not differ from ADT alone. ADT + ARPI was the most common second-line mCSPC and first-line mCRPC treatment. CONCLUSIONS: First-line ADT + ARPI was associated with significantly improved outcomes vs ADT alone in de novo mCSPC. These real-world results align with the benefits demonstrated in trials, supporting integration of TI with ARPIs into clinical practice to improve survival outcomes in patients with de novo mCSPC.

Duke Scholars

Author Thomas James Polascik Urology