Dr. Nguyen on Primary Analysis of the FORMULA-509 Trial in Prostate Cancer

Paul L. Nguyen, MD, senior physician, director, Genitourinary Clinical Center for Radiation Oncology, Dana-Farber Cancer Institute, professor of radiation oncology, Harvard Medical School, discusses primary findings from the phase 2 FORMULA-509 trial (NCT03141671) in prostate cancer.

The multicenter, open-label trial randomly assigned patients to receive salvage radiation with 6 months of a gonadotropin-releasing hormone (GnRH) with either bicalutamide or abiraterone acetate (Zytiga), apalutamide (Erleada), and prednisone (AAP), Nguyen begins.

Patients in this trial displayed detectable prostate-specific antigen (PSA) levels and unfavorable features after radical prostatectomy. The study’s primary end point was PSA progression-free survival (PFS), and the secondary end point was metastasis-free survival (MFS) as determined by conventional imaging techniques. Median follow-up occurred at 34 months.

The study was powered to detect a hazard ratio (HR) of 0.50 for PFS and 0.30 for MFS, Nguyen says. In the primary analysis of the trial, the 3-year PFS rate was 74.9% with AAP plus SOC regimenvs 68.5% with the SOC regimen alone. The 3-year MFS rate was 90.6% vs 87.2%, respectively. Associated HRs were 0.71 for PFS and 0.57 for MFS, Nguyen states. 

Although both PFS and MFS were numerically superior, they did not meet the prespecified threshold for statistical significance, Nguyen says. However, there is still a potential signal for survival benefit, Nguyen qualifies. Survival data may reach significance with longer follow-up, Nguyen adds.

Preplanned analyses of subgroups according to stratification factors were also conducted, Nguyen continues. Interestingly, the analysis showed that patients with a PSA level greater than 0.5 ng/mL experienced a statistically significant PFS and MFS benefit, he says. Moreover, the absolute improvement in MFS benefit was 18.2% at 3 years, which is a powerful effect size, Nguyen concludes. 

Editor’s Note: Dr. Nguyen reports serving as a consultant or in an advisory role for Bayer, Blue Earth Diagnostics, Boston Scientific, Janssen Oncology, Myovant Sciences; he reports receiving research funding from Astellas Pharma, Bayer, Janssen; he has stock and other ownership interests in Volatilyx (I).