"Evidence-based medicine" Asians are more likely to benefit from zoledronic acid?

Zoledronic acid (ZA) is often used as adjuvant therapy and bone-targeted therapy for metastatic castration-resistant prostate cancer (mCRPC), but the improvement of overall survival (OS) in patients with mCRPC with ZA is controversial
.
The efficacy of ZA in patients with the rest of the disease states of prostate cancer, such as hormone-sensitive prostate cancer (HSPC), metastatic hormone-sensitive prostate cancer (mHSPC), and non-metastatic castration-resistant prostate cancer (nmCRPC),
is also unclear.

In order to obtain evidence of the efficacy of ZA for different disease states of PCa, domestic researchers conducted systematic review and meta-analysis
of relevant literature in Chinese and English databases.

The study ultimately included results from 15 randomized controlled trials (RCTs) that received the ZA intervention, analysing
data from a total of 8280 patients with HSPC, mHSPC, nmCRPC and mCRPC.
The primary outcome was patient OS and secondary outcomes were bone-related events (SRE) and bone mineral density (BMD).

The investigators performed a meta-analysis
of data from 8280 patients with PCa (7856 non-Asian and 424 Asian) from Asia, Europe, North America and Oceania.
Of the 15 RCTs, seven, five and six studies reported data
on patients' OS, SRE and BMD.

Effect of ZA on OS in PCa patients

ZA failed to significantly improve OS in PCa patients compared with control (HR = 0.
95, 95% CI 0.
88 to 1.
03, P = 0.
19).

。 Subgroup analysis showed that ZA failed to significantly improve the HSPC group (HR=0.
96, 95%CI 0.
88-1.
05, P=0.
40), CRPC group (HR=0.
78, 95%CI 0.
46-1.
33, P=0.
36), M0 group (HR=0.
95, 95%CI 0.
81-1.
13, P=0.
59) and bone metastasis M1 group (HR=0.
85, 95%CI 0.
69-1.
04, P=).
0.
12) The patient's OS
.
Notably, the results of the race-divided subgroup analysis showed a significant improvement in OS in the Asian group who received the ZA intervention compared with the control group (HR = 0.
67, 95% CI 0.
48 to 0.
95, P = 0.
02), while there was no improvement in OS in the non-Asian group (HR = 0.
97, 95% CI 0.
90 to 1.
06, P = 0.
52).

Fig.
1 OS forest plot of patients in the ethnic subgroup

Effect of ZA on SRE in PCa patients

ZA significantly reduced the incidence of SRE compared to the control group (OR=0.
65, 95% CI 0.
45-0.
95, P=0.
02).

In subgroup analysis, the incidence of SRE was significantly reduced
in the M1 group with bone metastases (OR=0.
42, 95% CI 0.
24-0.
71, P=0.
001) and in the Asian group.

Effect of ZA on BMD in patients with PCa

Compared with the control group, ZA significantly improved the percentage of BMD (MD = 8.
08, 95% CI 5.
79-10.
37, P<0.
001).

A steady increase in the percentage of BMD values was also observed in the HSPC group (MD = 6.
65, 95% CI 5.
67-7.
62, P=0.
001).

Meta-analysis showed that ZA did not significantly improve OS in PCa patients with HSPC, CRPC, M0, or M1 status, but appeared to improve OS
in Asian patients.
Regardless of the patient's disease status, patients with PCa with bone metastases benefit from ZA, which not only significantly reduces the incidence of SRE, but also prevents bone loss at different stages of PCa and increases the patient's bone density percentage
.
Due to certain limitations, more RCTs will be needed in the future to assess the effect of
race on the efficacy of ZA.

References:

Chen C, Lin M, Yu D, et al.
Do disease status and race affect the efficacy of zoledronic acid in patients with prostate cancer? A systematic review and meta-analysis of randomized control trials.
PLoS One.
2022 Sep 22; 17(9):e0275176.