Poxvirus vaccine extended survival in castration-resistant metastatic prostate cancer

Patients with castration-resistant metastatic prostate cancer who were treated with a poxviral-based PSA-targeted vaccine — PROSTVAC-VF — had a significant survival extension compared to patients treated with a placebo, according to the results of a phase-2 study.

Although the study’s primary endpoint of PFS was not met, researchers observed an improvement in OS in those patients who received the vaccine.

PROSTVAC-VF vaccine (BN ImmunoTherapeutics) is a combination of two weakened poxviruses that have been genetically programmed to produce a slightly irregular version of PSA and three costimulatory molecules.

In the double blind study, 125 patients with prostate cancer who had not responded to hormone-lowering therapy were randomly assigned 2:1 to PROSTVAC-VF plus granulocyte-macrophage colony-stimulating factor (n=82) or placebo (n=40).

PFS was measured at two, four and six months. At six months, rates of PFS were similar between the two study arms.

However, the median OS of patients in the vaccine arm was 8.5 months longer than the placebo arm (25.1 months vs. 16.6 months; HR=0.56). At three years, 30.5% of the vaccine group was still alive vs. 17.5% of the placebo group.

Overall, the researchers wrote that the vaccine was well tolerated.

In an accompanying editorial, Eric J. Small, MD, and Lawrence Fong, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, Calif., wrote that the study “was successful as a hypothesis-generating exercise,” but that “it is premature to view these data as providing unambiguous evidence of clinical benefit.”

Kantoff PW. J Clin Oncol. 2010:doi:10.1200/JCO.2009.25.0597.

The publication of Kantoff and colleagues describes a carefully done study with provocative and encouraging results. This randomized phase-2 study indicates a survival advantage for PROSTVAC-VF in men with minimal symptoms and castration-resistant prostate cancer. Combined with similar findings (improved survival without objective or PSA responses) in studies of sipuleucel-T (autologous APCs, primed with prostatic acid phosphatase) data suggest an important effect of vaccine therapies in prostate cancer. These studies are extremely important and indicate potentially "heady days" for prostate cancer therapy - first new approaches in too long a time!

- Donald L. Trump, MD
HemOnc Today Editorial Board member