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A drug blocking the endothelin signal that prostate cancer uses in bone did not extend life, and it caused swelling, headaches and heart failure.
ENTHUSE M1 randomised 594 men with castration-resistant prostate cancer and bone metastases, pain-free or mildly symptomatic, 1:1 to zibotentan 10 mg daily or placebo added to standard treatment.
Median overall survival was 24.5 months with zibotentan and 22.5 months with placebo, hazard ratio 0.87 (95.2 percent confidence interval 0.69 to 1.10, p=0.240). No statistically significant difference was observed for any secondary efficacy endpoint, which included time to pain progression, time to chemotherapy, and time to new bone metastases.
Peripheral oedema (44 percent) and headache (31 percent) were the commonest adverse events with zibotentan, both direct consequences of endothelin A blockade. Cardiac failure of any grade occurred in 5.7 percent against 1.7 percent, and of grade 3 or worse in 3.0 against 1.0 percent, described as manageable and reversible.
The other two ENTHUSE trials, zibotentan with docetaxel and zibotentan in non-metastatic disease, were also negative, and AstraZeneca discontinued the programme in prostate cancer.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
594 randomised.
Confidence interval is 95.2 percent, as reported.
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (median)primary | Zibotentan 10 mg daily | 299 | 24.5 months | 0.87 (0.69 to 1.1) | 0.240 | link |
| Placebo | 295 | 22.5 months | ||||
| Cardiac failure, any grade | Zibotentan 10 mg daily | 299 | 5.7% | - | - | link |
| Placebo | 295 | 1.7% |
Shares SWOG S0421, Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC).
Shares Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.