The Current Role of Osteoclast Inhibitors in Patients with Prostate Cancer

Table 1

Main publications regarding ZA.

Reference	Study population	Treatment	End points
[22] RTOG 0518	CS M0	ZA 4 mg vs placebo	↑ BMD in lumbar spine (6% vs −5%, ), left total hip (1% vs −8%, ), and femoral neck (3% vs −8%, ); No prevention of bone fractures or QoL
[23]	CS M0, <1 year ADT	ZA vs placebo	↑ BMD in femoral neck by 3.6% (), hip by 3.8% (), and spine bone by 6.7% ()
[24] ZEUS 2015	PSA>20 ± LN+ ± gleason 8–10	ZA 4 mg + SOC vs SOC	Bone metastases: 14.7% in ZA vs 13.2% in placebo (); no protection from skeletal metastases
[25] STAMPEDE	CS, high-risk PCa (61% M1, 15% N+/M0, 24% N0M0,	ZA 4 mg + SOC vs SOC vs SOC + Doc vs SOC+ ZA +Doc	Median OS: NR for ZA + SOC vs 71 m for SOC vs 81 m for Doc + SOC vs 76 m for SOC + Doc + ZA; No increased survival for ZA; No delay of metastases for ZA
[26] GALBG 90202	CS M+	ZA 4 mg vs placebo	Similar time for new SRE: median time: 31.9 m for ZA vs 29.8 m for placebo (); no increased OS (HR: 0.88; 95% CI: 0.70–1.12, )
[27] ZAPCA	CS M+	ZA 4 mg + complete androgen blockade (CAB) vs CAB alone	Similar time to failure: 12.4 m vs 9.7 m (HR: 0.75, 95% CI: 0.57–1; ); ↑ time to new SRE for ZA + CAB (64.7 vs 45.9 m, HR: 0.58; 95 % CI 0.38–0.88; ); For PSA < 200, delay in treatment failure for ZA + CAB: 23.7 m vs 9.8 m (HR: 0.58, 95% CI: 0.35–0.93; )
[30]	CR M+	ZA 8 mg vs ZA 4 mg vs placebo	SRE for 4 mg ZA: 33.2% vs 44.2% placebo, 95% CI; −20.3% to −1.8%, ; SRE for 8 mg ZA: 38.5% vs 32.74% placebo, 95% CI; −15.1% to 3.6%, . ZA 4 (but not 8) mg: ↓ incidence of SRE, ↑ time to new SRE, ↓ pain score; No difference in PCa progression, PS & QoL
[31] (long term results of [30])	CR M+	ZA 4 mg vs placebo	↓ pts with SRE (38% for ZA vs 49%, 95% CI: −20.2% to −1.3%, p=0.28),; ↑ time to first SRE (448d for ZA vs 321, p=0.009), ↓ risk for SRE by 36% (risk ratio: 0.64, 95% CI: 0.485–0.845, p=0.002)
[32] TRAPEZE	CR M+/45% radiation therapy, median PSA: 146 mg/ml	Doc vs Doc + ZA 4 mg vs Doc + ZA + Strontium-89 (Sr)	Similar CPFS for Doc vs Doc + ZA: HR, 0.98; 95% CI, 0.85–1.14; ; similar OS for Doc vs Doc + ZA: HR, 0.99; 95% CI, 0.84–1.16;
[33] meta-analysis	18 RCT, CR M+	ZA vs control	Probably ↓ disease progression and ↓ SRE, with ZA, no effect in mortality, no effect in pair response; Concern for potential complications