Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223: a post hoc analysis of the REASSURE study.

Background: Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 (²²³Ra) treatment, but their association with treatment outcomes is unclear.

Methods: For patients with metastatic castration-resistant prostate cancer treated with ²²³Ra in the REASSURE study, we investigated whether ALP decline (Week 12) and/or pain response (during treatment) are associated with improved overall survival (OS). The Brief Pain Inventory-Short Form (BPI-SF) was used to assess pain at baseline and pain response (in patients with baseline BPI-SF score ≥2).

Results: Of 785 patients with baseline and Week 12 ALP measurements, 779 were eligible for the OS analyses. Overall, 80% of patients had an ALP decline. Median OS was longer in patients with than without an ALP decline (18.1 versus 14.2 months; HR 0.74; 95% CI 0.60-0.92). In patients with an ALP decline, there was no clear OS difference between those with versus without a pain response. For patients without ALP decline, median OS was longer in those with versus without a pain response (16.2 versus 10.9 months; HR 0.50; 95% CI 0.32-0.77).

Conclusions: Decreases in ALP and/or pain during ²²³Ra treatment are associated with improved OS. This may help support clinical decisions.

Clinical trial registration: ClinicalTrials.gov identifier NCT02141438. Analyses from the radium-223 REASSURE global study suggest that declines in alkaline phosphatase and pain during treatment may predict longer survival in patients with advanced prostate cancer and may help doctors make decisions with their patients.