PROSTVAC

PROSTVAC is a heterologous prime-boost vaccine: a vaccinia vector primes and a fowlpox vector boosts, both carrying the gene for prostate-specific antigen together with three co-stimulatory molecules (B7.1, ICAM-1 and LFA-3, known as TRICOM). It came from the National Cancer Institute and was licensed to Bavarian Nordic.

A randomised phase 2 trial reported a median overall survival 8.5 months longer than placebo, which is the kind of result that makes a phase 3 inevitable. PROSPECT randomised 1,297 men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer to PROSTVAC alone (432), PROSTVAC with granulocyte-macrophage colony-stimulating factor (432) or placebo (433).

At the third interim analysis the trial met its futility criteria and stopped. Median overall survival was 34.4 months with PROSTVAC alone (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 or death at 6 months were 29.4, 28.0 and 30.3 percent respectively.

The result is important beyond the drug. The phase 2 signal was an artefact of a placebo arm that did worse than the phase 3 placebo arm, which lived 34.3 months. Comparing a single-arm or small randomised result against a historical control in a disease where survival is long and improving is how this class of error happens.