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

Abstract Background Alkaline phosphatase (ALP) declines and pain responses can occur during radium-223 ( 223 Ra) treatment, but their association with treatment outcomes is unclear. Methods For patients with metastatic castration-resistant prostate cancer treated with 223 Ra 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 223 Ra treatment are associated with improved OS. This may help support clinical decisions. Clinical trial registration ClinicalTrials.gov identifier NCT02141438.