CRPC: Evidence

CRPC: VISION⁽¹⁾CRPC: TheraP⁽³⁾CRPC: CARD⁽⁵⁾CRPC: ALSYMPCA⁽⁶⁾

International, phase III trial

Population

Symptomatic CRPC
≥2 bone metastases
No known visceral metastases
Post-DOC, unfit for DOC or refused DOC

Design

Stratification factors: total ALP (< vs ≥220 U/l), bisphosphonate use, prior DOC

Endpoints

Primary endpoint: OS
Secondary endpoints:

Time to first SSRE
Biochemical endpoints

Ra-223 improved OS in progressive mCRPC patients with bone mets

Median time to... (mo)	Ra-223 + SOC (N=614)	PBO + SOC (N=307)	HR (95% CI)	P
OS	14.9	11.3	0.70 (0.58-0.83)	<0.001
1^st SSRE	15.6	9.8	0.66 (0.52-0.83)	<0.001
Increase in total alkaline phosphatase	7.4	3.8	0.17 (0.13-0.22)	<0.001
Increase in PSA level	3.6	3.4	0.64 (0.54-0.77)	<0.00

PEACE-3 phase III trial⁽⁷⁾: Ra-223 + ENZA vs ENZA alone in 1^st-line mCRPC and bone metastases

Adding Ra-223 improves rPFS (median rPFS: 19.4 vs 16.4 mo, P=0.0009)²
Bone fractures are a safety concern with hormonal treatment, especially for Ra-223 + ARPI

→ Co-administration of bone protecting agents (zoledronic acid or denosumab) should be offered^(7,8)

Adding Ra-223 resulted in:

Lower pain scores
Better QoL
Mild toxicity comparable to control arm, except for slightly higher haematologic toxicity and diarrhea

Key messages:

Adding Ra-223 to SOC improved efficacy outcomes and had a favourable safety profile
Co-administration of bone protecting agents should be offered^(7,8)

6. Parker C, Nilsson S, Heinrich D, et al. N Engl J Med 2013;369:213-23; 7. Tombal B, Choudhury A, Saad F, et al. Ann Oncol 2025;36:1058-67; 8. Gillessen S, Tombal B, Turco F, et al. Eur Urol 2025;87:285-88.