Adding the investigational therapeutic cancer vaccine PANVAC to docetaxel prolongs progression-free survival (PFS) in patients with metastatic breast cancer, a phase II study finds. [JAMA Oncol 2015, doi:10.1001/jamaoncol.2015.2736]

“Previous vaccine monotherapy trials have often failed to demonstrate improvements in short-term endpoints, such as PFS, despite improvements in long-term outcomes, such as overall survival. This may be explained by the lag between initial vaccination and eventual slowing of tumour growth rate,” wrote investigators of the study. “If this hypothesis is correct, then combining therapeutic cancer vaccines with standard-of-care agents may provide adequate time for the vaccines to take effect, resulting in improved PFS compared with the standard agents alone.”

In the study, 48 patients with metastatic breast cancer were randomized to receive docetaxel alone or in combination with PANVAC. Treatment was continued until disease progression or unacceptable toxicity.

The primary endpoint of PFS, although not statistically significant, favoured the combination arm (median, 7.9 months vs 3.9 months in the docetaxel-alone arm; hazard ratio, 0.65; p=0.09). “The statistical insignificance was likely owing to the small number of patients enrolled in this study,” the investigators noted.

Partial response was achieved in 16 percent of patients in the combination arm and 13 percent of patients in the docetaxel-alone arm.

The overall safety profile was comparable between the two arms, with the exception of significantly higher rates of injection site reactions (64 vs 0 percent; p<0.001) and oedema (44 vs 13 percent; p=0.02) in patients receiving PANVAC plus docetaxel. The investigators added, however, that the higher incidence of oedema observed in the combination arm was primarily due to the longer exposure to docetaxel as a result of prolonged PFS.

“We demonstrated that PANVAC can be safely combined with docetaxel to benefit patients with metastatic breast cancer,” they concluded. “These findings provide both a rationale and statistical assumptions for a larger definitive randomized study in a more uniform patient population.”

Patients who received PANVAC in this study were first given the priming vaccine PANVAC-V, followed by the monthly boosting vaccine PANVAC-F. With every vaccination, they also received an injection of granulocyte-macrophage colony-stimulating factor to boost the immune system.