No Benefit With Flutamide Plus Vaccine vs Flutamide Alone for Nonmetastatic CRPC

The treatment combination involving the androgen receptor antagonist flutamide given with the PROSTVAC vaccine was not associated with improved outcomes over flutamide alone in men with nonmetastatic castration-resistant prostate cancer (nmCRPC), according to results of a recent clinical trial. These trial results were presented in the journal The Oncologist.

PROSTVAC is a pox viral-based vaccine, involving T-cell costimulatory molecules, designed to target prostate-specific antigen (PSA). This multicenter, randomized phase 2 trial (ClinicalTrials.gov Identifier: NCT00450463) included patients with nmCRPC who were allowed to have received prior anti-androgen therapy.

The study had 2 treatment arms, with arm 1 receiving flutamide (250 mg) alone and arm 2 receiving flutamide (250 mg) plus PROSTVAC. PROSTVAC was administered as PROSTVAC-V (initial dose of 2×10⁸ plaque-forming units) followed by PROSTVAC-F, given every 28 days after PROSTVAC-V at a dose of 1×10⁹ plaque-forming units.

The primary study endpoint was the time to treatment failure. Secondary endpoints included immune responses and PSA responses.

A total of 33 patients were included in the flutamide-only arm, and 31 patients were in the flutamide plus PROSTVAC arm. Patient ages were a median 71.8 years and 69.8 years, respectively. All patients in both study arms had an Eastern Cooperative Oncology Group performance status of 0.

After a median potential follow-up of 46.7 months, the median time to treatment failure (TTF) was 4.5 months (range, 2 to 70) in the flutamide-only arm, compared with 6.9 months (range, 2.5 to 40) in the flutamide+PROSTVAC arm (P =.38). The primary endpoint was not met.

PSA response was greater than 50% in 7 patients from each study arm. Antigen-specific responses were seen in 58% of patients in the flutamide-only arm and in 56% of patients in the flutamide+PROSTVAC arm.

The study investigators considered both treatments to be well tolerated. Injection-site reaction was the most common side effect of a grade higher than 2. This occurred in 29 of the 31 patients receiving PROSTVAC and was self-limiting.

“Future studies may require a better understanding of how anti-androgens impact the immune system in order to develop immune combinations with optimal clinical efficacy,” the study investigators wrote in their report.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Madan RA, Bilusic M, Stein MN, et al. Flutamide with or without PROSTVAC in non-metastatic castration resistant (M0) prostate cancer. Oncologist. Published online May 3, 2023. doi:10.1093/oncolo/oyad058