PROSTVAC Ineffective For Metastatic CRPC (Open access)

Negative findings for the phase III trial of viral vector-based immunotherapy in castration-resistant prostate cancer patients with no or minimal symptoms

medwireNews: A trial of the viral vector-based immunotherapy PROSTVAC suggests the vaccine is well tolerated by men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC) but does not improve survival. 

As reported in the Journal of Clinical Oncology, the vaccine uses prostate-specific antigen (PSA) to generate a T-cell response against prostate cancer but the phase III study was stopped early after futility criteria were met at the third interim analysis. 

The trial participants were stratified by PSA and lactate dehydrogenase levels at screening and given one of three different treatments on weeks 1, 3, 5, 9, 13, 17 and 21, followed by standard of care therapy. 

The primary endpoint of median overall survival was a comparable 34.4 months for the 432 patients randomly assigned to receive PROSTVAC, 33.2 months for the 432 patients given PROSTVAC plus granulocyte–macrophage colony stimulating factor (GM-CSF), and 34.3 months for the 433 patients given placebo. 

The proportion of patients alive without radiographic or pain progression, or chemotherapy initiation at 6 months was also similar in the PROSTVAC, PROSTVAC plus GM-CSF, and placebo arms, at 29.4%, 28.0% and 30.3%, respectively. 

James Gulley, from the National Institutes of Health in Bethesda, Maryland, USA, and co-authors write that PROSTVAC was “safe and well tolerated with no unexpected TEAEs [treatment-emergent adverse events]”. 

More than 75% of TEAEs reported were grade 1, with only 0.9–3.0% considered related to treatment. However, treatment-related AEs were more common with PROSTVAC plus GM-CSF than with PROSTVAC alone or placebo (any grade, 79.3% vs 72.7% and 70.6%, respectively) and this was particularly true for pyrexia and injection site reactions. 

“[W]e observed that vaccines induce T cells that are capable of infiltrating tumors, but that this immune response does not translate into clinical benefit poses a major challenge to the immunotherapy community”, the researchers comment.

“Historical data have shown that PROSTVAC is capable of generating specific T-cell responses against PSA as well as cascade antigens, indicating that the poxvirus platform has the potential to induce clinical benefit in the right context—that is, with different antigen targets, in other disease settings, and in combination with checkpoint inhibition”, they believe.

The team adds: “This possibility is being evaluated in ongoing clinical trials.” 



Gulley JL, Borre M, Vogelzang NJ, et al. Phase III trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer . J Clin Oncol; Advance online publication 28 February 2019.
doi: 10. 1200/JCO.18.02031

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