SRT plus GnRH agonist with acetate/prednisone, apalutamide improves prostate cancer survival
Postoperative salvage radiotherapy (SRT) plus 6 months of androgen deprivation therapy (ADT) with abiraterone acetate/prednisone (AAP) and apalutamide (Apa) results in better progression-free (PFS) and metastasis-free survival (MFS) among patients with prostate cancer, findings from FORMULA-509 have shown. However, the primary analysis did not reach the prespecified threshold for statistical significance.
In addition, such improvements were most prominent in the subgroup of patients with prostate specific antigen (PSA) >0.5, where a preplanned subgroup analysis by stratification factors achieved a statistically significant benefit for both PFS and MFS.
An investigator-initiated, multicentre, open-label, randomized trial, FORMULA-509 was recently presented at the 2023 ASCO GU Cancers Symposium by lead researcher Paul L. Nguyen from the Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, US.
Nguyen and his team recruited a total of 345 patients with PSA ≥0.1 following radical prostatectomy (RP) and one or more unfavourable features (eg, Gleason 8-10, PSA>0.5, pT3/T4, pN1 or radiographic N1, PSA doubling time <10 months, negative margins, persistent PSA, gross local/regional disease, or Decipher High Risk). Of these, 332 were eligible for analysis.
Patients were treated with SRT plus 6 months of GnRH agonist and were then randomized to concurrent bicalutamide 50 mg (n=172) or AAP 1,000 mg/5 mg plus Apa 240 mg QD (n=173). Radiation to pelvic nodes was required for pN1 and optional for pN0.
“The study was powered to detect a hazard ratio (HR) of 0.50 for PFS and an HR of 0.30 for MFS, each with 80-percent power and one-sided type I error of 0.05,” the researchers said. “Stratification was by PSA at study entry (>0.5 vs ≤0.5) and pN0 vs pN1. Analyses within these subgroups were preplanned.”
Of the patients, 29 percent were pN1, and 31 percent had PSA >0.5 ng/mL. The researchers followed them for a median of 34 months.
PFS at 3 years was higher with AAP plus Apa compared with bicalutamide (74.9 percent vs 68.5 percent; HR, 0.71, 90 percent confidence interval [CI], 0.49‒1.03; stratified one-sided log-rank p=0.06). MFS was also higher with AAP plus Apa vs bicalutamide (90.6 percent vs 87.2 percent; HR, 0.57, 90 percent CI, 0.33‒1.01; stratified one-sided log-rank p=0.05). [ASCO GU 2023, abstract 303]
Preplanned analysis by stratification factors revealed that survival benefits with AAP/Apa were greater for patients with PSA >0.5. At 3 years, PFS was 67.2 percent with AAP plus Apa vs 46.8 percent with bicalutamide (HR, 0.50, 90 percent CI, 0.30‒0.86; p=0.03, while MFS was 84.3 percent and 66.1 percent, respectively (HR, 0.32, 90 percent CI, 0.15‒0.72; p=0.01).
“No statistically significant benefit was detected in preplanned analyses of stratification subgroups defined by PSA ≤0.5, pN0, or pN1,” the researchers said.
In addition, adverse events were consistent with established safety profiles of the study drugs. Rashes and hypertension occurred more frequently among patients treated with AAP plus Apa.
“Six months of a GnRH agonist with SRT is a standard of care for patients with unfavourable features and a detectable PSA post-RP,” the researchers noted. “FORMULA-509 was designed to evaluate whether adding 6 months of AAP and Apa to this regimen could improve outcomes.”