The Effect of a Flutamide-PROSTVAC Combination in nmCRPC

PROSTVAC is an active immunotherapy vaccine that contains prostate-specific antigen (PSA) to create a T-cell response against prostate cancer. The androgen receptor antagonist (ARA) flutamide, which was approved by the US Food and Drug Administration in 1989 as the first nonsteroidal antiandrogen drug, is used to inhibit prostate cancer cell growth.

A multicenter, randomized clinical trial sought to determine if flutamide is more effective with or without the addition of PROSTVAC in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The results were published in The Oncologist.

Patients who were eligible for the study had negative computed tomography scans and Tc99 bone scans, along with rising PSA levels on androgen deprivation therapy. Patients were also evaluated for antigen-specific immune responses through intracellular cytokine staining. Prior ARA treatment was a stratification factor.

A total of 64 patients were included in the study. Flutamide was administered to 33 patients with a median age of 71.8 years, while flutamide plus PROSTVAC was administered to 31 patients with a median age of 69.8 years. After a median potential follow-up period of 46.7 months, the median time to treatment failure was 4.5 months for flutamide alone and 6.9 months for flutamide plus PROSTVAC.

In each treatment arm, 7 patients had a PSA response >50%. Antigen-specific responses were similar in both arms, occurring in 58% of patients who received flutamide alone and in 56% of patients who received flutamide plus PROSTVAC. Both treatments were well-tolerated. The most common side effect greater than grade 2 was injection site reaction, which was observed in 29 of the patients who received flutamide plus PROSTVAC.

Overall, the combination treatment of flutamide and PROSTVAC did not improve outcomes in patients with nmCRPC. The investigators noted that future studies “may require a better understanding of how antiandrogens impact the immune system in order to develop immune combinations with optimal clinical efficacy.”