PROSPECT

PROSPECT randomised 1,297 men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer to PROSTVAC (432), PROSTVAC with granulocyte-macrophage colony-stimulating factor (432) or placebo (433), with three planned interim analyses.

At the third interim analysis the futility criteria were met and the trial stopped early. Neither active arm affected overall survival: median 34.4 months with PROSTVAC, hazard ratio 1.01 (95 percent confidence interval 0.84 to 1.20, p=0.47); 33.2 months with the granulocyte-macrophage colony-stimulating factor combination, 1.02 (0.86 to 1.22, p=0.59); and 34.3 months with placebo. Patients alive without radiographic progression, pain progression, chemotherapy initiation or death at 6 months were 29.4, 28.0 and 30.3 percent respectively.

Adverse events were similar across arms, injection site reactions in 62 to 72 percent and fatigue in 21 to 24 percent, with arrhythmias the commonest cardiac event at 1.4 to 3.5 percent. No myocarditis or pericarditis was reported and serious treatment-related events occurred in under 1 percent of all patients.

The phase 2 result that justified the trial had reported a median overall survival 8.5 months longer than placebo. In PROSPECT the placebo arm lived 34.3 months, far longer than the phase 2 control, which is the likeliest explanation: the earlier comparison was against an unrepresentatively poor control group.