For patients with detectable prostate-specific antigen (PSA) after radical prostatectomy, 6 mo of a GNRH agonist with salvage radiotherapy (sRT) is a standard treatment option.
FORMULA-509 (NCT03141671) enrolled 345 patients with PSA ≥0. 1 ng/ml and high-risk features from November 24, 2017 to March 25, 2020. Patients received sRT plus 6 mo of a GNRH agonist and randomization to bicalutamide (50 mg) or abiraterone acetate + prednisone (AAP; 1000 mg/5 mg) + apalutamide (240 mg) QD. The primary endpoint was PSA progression-free survival (PFS). A secondary endpoint was metastasis-free survival (MFS) on conventional imaging. Stratification was by PSA (>0.5 vs ≤0.5 ng/ml) and pN status (pN0 vs pN1).
Median follow-up was 34 mo. AAP + apalutamide did not reach the prespecified significance level for PFS benefit in comparison to bicalutamide (hazard ratio [HR] 0.71. 90% confidence interval [CI] 0.49-1.03; stratified one-sided log-rank p = 0.063), with 3-yr PFS rates of 68.5% with bicalutamide versus 74.9% with AAP + apalutamide. The HR for MFS was 0.57 (90% CI 0.33-1.01; stratified one-sided p = 0.050) and the 3-yr MFS rates were 87.2% with bicalutamide versus 90.6% with AAP + apalutamide. A preplanned analysis by stratification factors revealed that for patients with PSA >0.5 ng/ml, AAP + apalutamide was associated with superior PFS (HR 0.50, 95% CI 0.27-0.95; 2-sided p = 0.030; 3-yr PFS 46.8% with bicalutamide vs 67.2% with AAP + apalutamide) and MFS (HR 0.32, 95% CI 0.13-0.84; 2-sided p = 0.014; 3-yr MFS 66.1% with bicalutamide vs 84.3% with AAP + apalutamide). Adverse events were consistent with the known safety profiles of the study agents, with more frequent rash and hypertension in the AAP + apalutamide arm.
This study did not reveal a benefit for the overall population, but addition of AAP + apalutamide (vs bicalutamide) to sRT and ADT improved PFS and MFS in the prespecified subgroup with PSA >0.5 ng/ml.
European urology. 2026 Feb 10 [Epub ahead of print]
Paul L Nguyen, Marisa A Kollmeier, Dana E Rathkopf, Karen E Hoffman, Amado J Zurita, Daniel E Spratt, Robert T Dess, Stanley L Liauw, Russell Z Szmulewitz, David J Einstein, Glenn J Bubley, James B Yu, Yi An, Anthony C Wong, Felix Y Feng, Rana R McKay, Brent S Rose, Kee-Young Shin, Adam S Kibel, Mary-Ellen Taplin
Brigham and Women's Hospital, Boston, MA, USA. Electronic address: ., Memorial Sloan Kettering Cancer Center, New York, NY, USA., University of Texas MD Anderson Cancer Center, Houston, TX, USA., University Hospitals Cleveland Medical Center, Cleveland, OH, USA., University of Michigan Medicine, Ann Arbor, MI, USA., Mass General Brigham Cancer Center, Chicago, IL, USA., Beth Israel Deaconess Medical Center, Boston, MA, USA., Dartmouth Hitchcock Medical Center, Lebanon, NH, USA., Yale University School of Medicine, New Haven, CT, USA., UCSF Cancer Center, University of California-San Francisco, San Francisco, CA, USA., University of Chicago Medicine, Moores Cancer Center, La Jolla, CA, USA., Dana-Farber Cancer Institute, Boston, MA, USA., Brigham and Women's Hospital, Boston, MA, USA.