(UroToday.com) The 2023 GU ASCO annual meeting included an oral abstract prostate cancer session, featuring a presentation by Dr. Paul Nguyen discussing results of the FORMULA-509 trial, a multicenter randomized trial of post-operative salvage radiotherapy and 6 months of GnRH agonist with or without abiraterone acetate/prednisone and apalutamide post-radical prostatectomy. GETUG-16 established that six months of a GnRH agonist with salvage radiotherapy is a standard of care for patients with unfavorable features and a detectable PSA post- radical prostatectomy.1 The FORMULA-509 trial was designed to evaluate whether adding six months of abiraterone acetate/prednisone and apalutamide to this regimen could improve outcomes.
FORMULA-509 (NCT03141671) is an investigator-initiated, multi-center, open-label, randomized trial. Patients had to have a PSA≥0.1 ng/mL post-radical prostatectomy and one or more unfavorable features (Gleason 8-10 disease, PSA>0.5 ng/mL, pT3/T4, pN1 or radiographic N1, PSA doubling time <10 months, negative margins, persistent PSA, gross local/regional disease, or Decipher High Risk). All patients received salvage radiotherapy plus 6 months of GnRH agonist and randomization was to concurrent bicalutamide 50 mg or abiraterone acetate/prednisone 1000mg/5mg + apalutamide 240mg daily. Radiation to the pelvic nodes was required for pN1 and optional for pN0 disease. The primary endpoint was PSA progression-free survival and a secondary endpoint was metastasis-free survival determined by conventional imaging. The trial design of FORMULA-509 is as follows:
The study was powered to detect a HR of 0.50 for progression-free survival and a HR of 0.30 for metastasis-free survival, each with 80% power and one-sided type I error of 0.05. Stratification was by PSA at study entry (>0.5 ng/mL vs.≤0.5 ng/mL) and pN0 vs pN1, and analyses within these subgroups were pre-planned.
There were 345 participants (332 evaluable) from 9 sites that were randomized from November 24, 2017 to March 25, 2020, including 172 to bicalutamide and 173 to abiraterone acetate/prednisone/apalutamide. The median follow-up was 34 (6-53) months, 29% were pN1, and 31% had a PSA >0.5 ng/mL. The full patient characteristics are as follows:
The HR for progression-free survival was 0.71 (90% CI 0.49-1.03), stratified one-sided log-rank p=0.06 (3-year progression-free survival was 68.5% bicalutamide vs 74.9% abiraterone acetate/prednisone /apalutamide):
The HR for metastasis-free survival was 0.57 (90% CI 0.33-1.01), stratified one-sided log rank p=0.05 (3-year metastasis-free survival was 87.2% bicalutamide vs 90.6% abiraterone acetate/prednisone/apalutamide):
In a pre-planned analysis by stratification factors, abiraterone acetate/prednisone/apalutamide was significantly superior for patients with PSA >0.5 ng/mL for progression-free survival [HR 0.50, (90% CI 0.30-0.86), p=0.03 (2-sided); 3-year progression-free survival 46.8% bicalutamide vs. 67.2% abiraterone acetate/prednisone/apalutamide]:
and for metastasis-free survival [HR 0.32 (90% CI 0.13-0.84), p=0.02 (2-sided); 3-year metastasis-free survival 66.1% bicalutamide vs. 84.3% abiraterone acetate/prednisone/apalutamide]:
There was no statistically significant benefit detected in pre-planned analyses of stratification subgroups defined by PSA ≤0.5 ng/mL, pN0, or pN1:
Adverse events were consistent with the known safety profiles of the agents being studied, with more rash and hypertension in the abiraterone acetate/prednisone/apalutamide arm.
Dr. Nguyen concluded his presentation discussing results of the FORMULA-509 trial with the following take-home messages:
- Although this primary analysis did not meet the pre-specified threshold for statistical significance, it does strongly suggest that the addition of abiraterone acetate/prednisone/apalutamide to salvage radiotherapy + 6 months of ADT may improve progression-free survival and metastasis-free survival
- This may be particularly evident in the subgroup of patients with PSA>0.5 ng/mL where a pre-planned subgroup analysis by stratification factors observed a statistically significant benefit for both progression-free survival and metastasis-free survival
- Six months of intensified ADT with next generation anti-androgens may provide an attractive alternative to lengthening ADT for patients with rising PSA and unfavorable features after radical prostatectomy
Clinical trial information: NCT03141671
Presented by: Paul L. Nguyen, MD, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
Co-Authors: Marisa Kollmeier, Dana E. Rathkopf, Karen E. Hoffman, Amado J. Zurita, Daniel Eidelberg Spratt, Robert Timothy Dess, Stanley L. Liauw, Russell Zelig Szmulewitz, David Johnson Einstein, Glenn 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
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.
References:
- Carrie C, Hasbini A, de Laroche G, et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): A randomized, multicentre, open-label phase 3 trial. Lancet Oncol 2016;17(6):747-756