Efficacy and safety of docetaxel (D) vs androgen-receptor signaling inhibitors (ARSi) as second-line therapy (Rx) after progression on alternative ARSi as first-line Rx for patients who are elderly (≥75 years old) with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter international database: A SPARTACUSS–Meet-URO 26 study.

Abstract

166 Background: About 2/3 of all prostate cancer (PCa) deaths occur in patients aged ≥75, who are frequently diagnosed with advanced PCa. ARSi abiraterone acetate (AA) and enzalutamide (E) are the most common 1st line Rx for patients with mCRPC. Yet, the optimal treatment sequence for the elderly ≥75 after ARSi failure is still unclear. Methods: Using available medical records, patients aged ≥75 who started ARSi as 1st line Rx for mCRPC within January 2015 - April 2019 and, upon progression, 2nd line alternative ARSi or D were identified from the IRB approved hospital registries of 10 centers in Europe, North and South America. Patients were categorized by type of 2nd line Rx for mCRPC into cohorts AA/E and D. Primary endpoints were overall survival (OS) from 1st line AA/E start, OS and radiographic progression-free survival (rPFS) from 2nd line Rx start, and safety. The Kaplan Meier method was used to calculate endpoint distributions and medians (95% CI). Results: Of the 122 patients identified, 57 (46.7%) had AA/E and 65 (53.3%) D, as 2nd line Rx for mCRPC. Median follow-up was 26.3 months (95% CI, 23.1-27.9 months). Cohort AA/E tended to be older (81 vs 78 years; p=0.001) and with high-volume disease (45.5% vs 25.0%; p=0.022) compared to cohort D. No significant difference in OS from 1st line ARSi onset and OS or rPFS from 2nd line Rx start was found between the 2 cohorts. Cohort AA/E had longer rPFS than cohort D, albeit not significant (18.5 vs 12.0 months; p=0.13). Rates of adverse events (AEs) of any grade (42.1 vs 53.8; p=0.21) and AEs of grade ≥3 (19.3% vs 18.5%; p=1.0) did not show significant differences between the 2 cohorts. Conclusions: Within the limitations of small cohorts and retrospective design, treatment sequences with 2nd line AA/E or D after failure of 1st line alternative ARSi for mCRPC showed similar efficacy and safety in the elderly ≥75 years old.