Assessment with a genomic test could help predict which patients with recurrent prostate cancer are most likely to benefit from the addition of hormonal therapy to radiation following prostatectomy, according to findings from the phase II BALANCE trial (NRG GU006) presented in a press briefing during the American Society for Radiation Oncology (ASTRO) 67th Annual Meeting (Abstract LBA 04).
This was the first randomized trial to validate the biomarker tool PAM50 to guide decision-making for use of apalutamide. The novel tool determines which patients with recurrent prostate cancer have luminal B subtype tumors or not, as these patients were likely to respond well to hormonal therapy.
“We’ve been searching for decades for a way to determine which patients are most likely to respond to hormone therapy after prostatectomy,” stated principal investigator Daniel Spratt, MD, Professor and Chair of Radiation Oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University School of Medicine. “We now have a tool that lets us tailor treatment based on a tumor’s biology and recommend hormone therapy only for those patients who we think can expect to see a benefit.”
Rationale and Study Methods
Hormonal therapy is a common addition to radiation therapy for patients whose prostate-specific antigen (PSA) levels are still rising after prostatectomy. However, it is associated with several significant adverse effects, including bone loss, metabolic changes, and cardiovascular risks. As such, investigators have looked for ways to limit the use of hormonal therapy to patients who would experience the most benefit.
“Testosterone is important for maintaining bone, muscle, cognitive, and cardiac health, but it’s also the key fuel driving prostate tumors,” said Dr. Spratt. “Until now, we haven’t had a reliable way to tell who really needs hormone therapy and who does not.”
The PAM50 subtyping gene expression test was developed for use in breast cancer before being adapted by Dr. Spratt and colleagues for use in prostate cancer.
The BALANCE trial was a phase II biomarker-stratified, randomized trial of salvage radiotherapy with or without apalutamide in patients with PSA levels between 0.1 and 1.0 ng/mL and without evidence of nodal or distant metastasis following radical prostatectomy. All patients (n = 295) were randomly assigned to receive stereotactic radiation therapy with placebo or apalutamide at 240 mg daily for 6 months. Stratification was based on PAM50 molecular subtype of luminal B or non‒luminal B.
Key Study Findings
In the study, 43% of patients had the luminal B subtype. Patients with luminal B tumors who received apalutamide demonstrated a significant improvement in biochemical progression-free survival (hazard ratio [HR] = 0.80; 80% confidence interval [CI] = 0.29‒0.68; one-sided P = .0062). The 5-year estimated rates of biochemical progression-free survival were 72.4% in the apalutamide arm and 53.9% in the placebo arm. Patients with non‒luminal B tumors did not achieve significant benefit in biochemical progression-free survival from the addition of hormonal therapy (HR = 0.95; 80% CI = 0.65‒1.41; P = .44). The 5-year rates of biochemical progression-free survival were 70.2% with and 71.1% without apalutamide.
“The patients with luminal B tumors saw a large benefit, both in reducing recurrence and lowering the risk of metastatic disease,” said Dr. Spratt. “But for patients without this subtype, hormone therapy didn’t change the outcome. That’s incredibly valuable information when we’re trying to personalize care.”
Metastasis-free survival was also improved with the use of apalutamide in patients with luminal B subtype (HR = 0.27; 95% CI = 0.07‒0.95; P = .029). At 5 years, rates of metastasis-free survival were 94.7% with apalutamide and 81.8% with placebo. In patients with non‒luminal B tumors, no benefit was seen in metastasis-free survival (HR = 1.06; 95% CI = 0.41‒2.78; P = .90). Five-year metastasis-free survival rates were 89.9% and 89.3% with and without apalutamide, respectively.
Grade 3 or higher gastrointestional toxicities were reported in 5.7% of patients in the apalutamide arm and in 2.6% of patients in the placebo arm, and genitourinary effects were observed in 3.5% of patients in the apalutamide arm and in 4.5% of patients in the placebo arm. Grade 3 or higher rash was reported in 5% of patients in the apalutamide arm and breast pain was observed in 0.7% of patients.
“[This] gives us a promising way to personalize care, recommending hormone therapy for those who respond, and avoiding unnecessary treatment when it is unlikely to help,” Dr. Spratt said.
Disclosure: The study was funded with support from the National Cancer Institute. For full disclosures of the study authors, visit amportal.astro.org.
