Research frontiers Efficacy and safety of radium-223 in patients with mCRPC with asymptomatic bone metastases

Patients with prostate cancer (PCa) with distant metastases have lower 5-year survival rates, while bone metastases are the most common site of distant metastases
.
A recent article published in the European Journal of Cancer explores the treatment of this type of patient, and the medical pulse is summarized as follows
.

Radium-223 in combination with abitron, enzalumide, or desulumab has been found to improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases (BMS), especially in asymptomatic bone metastases
.
Androgen receptor V7 (AR-V7) is an independent predictor of mCRPC prognosis, but the association between radium-223 efficacy and AR-V7 expression is not known
.
In light of this, this study aimed to assess the efficacy and safety of radium-223 in patients with mCRPC with asymptomatic BMS who progressed after first-line androgen deprivation therapy (ADT) and to explore the link between the
efficacy of radium-223 and AR-V7 expression.

EXCAAPE (NCT03002220) is a multicenter, single-armed, open-label, uncontrolled Phase IIa trial of 52 patients with mCRPC with asymptomatic BMS who developed progress after treatment with
abiraterone or enzalumine.
Patients receive up to 6 months of radium-223 treatment (55 kBq per kilogram of body weight every 4 weeks
).
The primary endpoint was radiographically progression-free survival (rPFS), while the secondary study endpoints included rPFS, total survival (OS), and safety
based on AR-V7 expression in circulating tumor cells (CTCs).

The median follow-up time was 6.
6 months (1.
3 to 18.
2) and the median rPFS was 5.
5 months (95% CI 5.
3 to 5.
5, P=0.
025).

The median rPFS in AR-V7(−) patients was longer than in AR-V7(+) patients, but the difference was not statistically significant (5.
5 months vs 2.
2 months, P=0.
056).

The median OS in AR-V7(−) patients was 14.
8 months (95% CI 11.
2-not achieved), significantly longer than in AR-V7(+) patients (14.
8 vs 3.
5 months, P<0.
01).
<b12>

Figure 1 rPFS based on AR-V7 expression

RAX-223 is well tolerated, with the most common grade 3/4 adverse events being anaemia (5.
8%) and thrombocytopenia (11.
5%)
.

Overall, radium-223 may be a safe and effective treatment for patients with mCRPC with asymptomatic BMS who progress after first-line androgen deprivation therapy (ADT
).
AR-V7 expression in CTCs is significantly associated with the patient's OS and is not related to
rPFS.
Due to the small sample size, this result
should be further validated in larger studies in the future.

References:

Carles J, Alonso-Gordoa T, Mellado B, et al.
Radium-223 for patients with metastatic castration-resistant prostate cancer with asymptomatic bone metastases progressing on first-line abiraterone acetate or enzalutamide: A single-arm phase II trial.
Eur J Cancer.
2022 Sep; 173:317-326.

Editor: Wang Mumu

Reviewer: LR

Execution: Wang Mumu