Phase III data show no support for PROSTVAC in mCRPC
medwireNews: A phase III trial investigating the efficacy of PROSTVAC, a viral vector–based immunotherapy, in the treatment of metastatic castration-resistant prostate cancer (mCRPC) was stopped early due to a lack of positive results, say researchers.
The findings “did not support the positive signal from the randomized phase II study” in which PROSTVAC “prolonged median overall survival (OS) by 8.5 months versus placebo,” write James Gulley (National Institutes of Health, Bethesda, Maryland, USA) and co-authors.
They explain: “PROSTVAC is an active immunotherapy vaccine that contains prostate-specific antigen (PSA) as the tumor-associated antigen used to generate a T-cell response against prostate cancer.”
In the current study, median OS was 34.4 months among the 432 patients with mCRPC randomly assigned to receive PROSTVAC and 33.2 months among the 432 patients assigned to receive PROSTVAC plus granulocyte-macrophage colony-stimulating factor.
By comparison median OS was 34.3 months among the 433 patients who received placebo, which was not significantly different from either treatment arm, Gulley et al report in the Journal of Clinical Oncology.
There were also no significant differences between the groups in the proportion of patients alive without events – namely, radiographic progression, pain progression, chemotherapy initiation, or death – at 6 months, at 29.4%, 28.0% and, 30.3%, for PROSTVAC, PROSTVAC plus granulocyte-macrophage colony-stimulating factor, and placebo, respectively.
Discussing the reasons for the different outcomes between the phase II and phase III trials, the investigators speculate that the earlier study may have “generated a false-positive signal as a result of being underpowered for an OS comparison.”
They also point out that at the time of the phase II trial, docetaxel was the only life-prolonging treatment available, whereas many more, such as cabazitaxel, sipuleucel-T, abiraterone acetate, enzalutamide, and radium-223, had been approved ahead of the phase III trial.
“It is possible that these life-prolonging therapies negatively affected the likelihood of this trial achieving positive results,” Gulley and team remark, noting that median OS in the placebo group was 3 years.
Nonetheless, PROSTVAC was “safe and well tolerated” in line with the results of earlier studies, but “[t]he observed lack of clinical signal suggests that either the immune responses generated in this study were not sufficient or there were other negative regulatory influences in the tumor microenvironment that prevented clinically relevant immune-mediated killing,” say the authors.
They conclude: “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.
“This possibility is being evaluated in ongoing clinical trials.”
By Laura Cowen
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