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: Clinical Studies

Joe M. O’Sullivan; Daniel Heinrich; Elena Castro; Saby George; Sabina Dizdarevic; Sergio Baldari; Markus Essler; Igle Jan de Jong; Secondo Lastoria; Peter G. Hammerer; Bertrand Tombal; Nicholas D. James; Jeff Meltzer; Per Sandström; Oliver Sartor

doi:10.1038/s41416-024-02927-w

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: Clinical Studies

Joe M. O’Sullivan^*, Daniel Heinrich, Elena Castro, Saby George, Sabina Dizdarevic, Sergio Baldari, Markus Essler, Igle Jan de Jong, Secondo Lastoria, Peter G. Hammerer, Bertrand Tombal, Nicholas D. James, Jeff Meltzer, Per Sandström, Oliver Sartor

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	101993
Number of pages	7
Journal	British Journal of Cancer
Volume	132
DOIs	https://doi.org/10.1038/s41416-024-02927-w
Publication status	Published - 9-Mar-2025

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O’Sullivan, J. M., Heinrich, D., Castro, E., George, S., Dizdarevic, S., Baldari, S., Essler, M., de Jong, I. J., Lastoria, S., Hammerer, P. G., Tombal, B., James, N. D., Meltzer, J., Sandström, P., & Sartor, O. (2025). 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: Clinical Studies. British Journal of Cancer, 132, Article 101993. https://doi.org/10.1038/s41416-024-02927-w

@article{39251c666a704741b61b72d3d62b37d1,

title = "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: Clinical Studies",

abstract = "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.",

author = "O{\textquoteright}Sullivan, {Joe M.} and Daniel Heinrich and Elena Castro and Saby George and Sabina Dizdarevic and Sergio Baldari and Markus Essler and {de Jong}, {Igle Jan} and Secondo Lastoria and Hammerer, {Peter G.} and Bertrand Tombal and James, {Nicholas D.} and Jeff Meltzer and Per Sandstr{\"o}m and Oliver Sartor",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = mar,

day = "9",

doi = "10.1038/s41416-024-02927-w",

language = "English",

volume = "132",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

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O’Sullivan, JM, Heinrich, D, Castro, E, George, S, Dizdarevic, S, Baldari, S, Essler, M, de Jong, IJ, Lastoria, S, Hammerer, PG, Tombal, B, James, ND, Meltzer, J, Sandström, P & Sartor, O 2025, '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: Clinical Studies', British Journal of Cancer, vol. 132, 101993. https://doi.org/10.1038/s41416-024-02927-w

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: Clinical Studies. / O’Sullivan, Joe M.; Heinrich, Daniel; Castro, Elena et al.
In: British Journal of Cancer, Vol. 132, 101993, 09.03.2025.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Alkaline phosphatase decline and pain response as predictors of overall survival benefit in patients treated with radium-223

T2 - a post hoc analysis of the REASSURE study: Clinical Studies

AU - O’Sullivan, Joe M.

AU - Heinrich, Daniel

AU - Castro, Elena

AU - George, Saby

AU - Dizdarevic, Sabina

AU - Baldari, Sergio

AU - Essler, Markus

AU - de Jong, Igle Jan

AU - Lastoria, Secondo

AU - Hammerer, Peter G.

AU - Tombal, Bertrand

AU - James, Nicholas D.

AU - Meltzer, Jeff

AU - Sandström, Per

AU - Sartor, Oliver

PY - 2025/3/9

Y1 - 2025/3/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85217232652&partnerID=8YFLogxK

U2 - 10.1038/s41416-024-02927-w

DO - 10.1038/s41416-024-02927-w

M3 - Article

C2 - 39789153

AN - SCOPUS:85217232652

SN - 0007-0920

VL - 132

JO - British Journal of Cancer

JF - British Journal of Cancer

M1 - 101993

ER -

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: Clinical Studies

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