Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer

Oncologist. 2023 Jul 5;28(7):642-e561. doi: 10.1093/oncolo/oyad058.

Abstract

Background: Before 2018, there was no standard of care for non-metastatic (M0) castration resistant prostate cancer nmCRPC. Androgen receptor antagonists (ARAs) were commonly used sequentially nmCRPC.

Methods: This was a multicenter, randomized clinical trial comparing the ARA flutamide+/-PROSTVAC, a pox viral vaccine targeting PSA that includes T-cell co-stimulatory molecules. Eligible men had negative CT and Tc99 bone scans, and rising PSA on ADT. Previous treatment with ARA was a stratification factor. Patients were also evaluated for antigen-specific immune responses using intracellular cytokine staining.

Results: Thirty-three patients randomized to flutamide and 31 to flutamide+vaccine. The median age was 71.8 and 69.8 years, respectively. The median time to treatment failure after a median potential follow-up of 46.7 months was, 4.5 months (range 2-70) for flutamide alone vs. 6.9 months (2.5-40; P = .38) with flutamide+vaccine. Seven patients in each arm had a >50% PSA response. Antigen-specific responses were similar in both arms (58% of patients in flutamide alone and 56% in flutamide+vaccine). The treatments were well tolerated. The most common side effect > grade 2 was injection site reaction seen in 29/31 vaccine patients which were self-limiting.

Conclusion: The combination of flutamide+PROSTVAC did not improve outcomes in men with nmCRPC compared with flutamide alone. (ClinicalTrials.gov Identifier: NCT00450463).

Keywords: anti-androgen therapy; cancer vaccine; immunotherapy; prostate cancer.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / therapeutic use
  • Castration
  • Flutamide / adverse effects
  • Flutamide / therapeutic use
  • Humans
  • Male
  • Prostate-Specific Antigen
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / pathology

Substances

  • Flutamide
  • PROSTVAC
  • Prostate-Specific Antigen
  • Androgen Antagonists

Associated data

  • ClinicalTrials.gov/NCT00450463