PAM50 biomarker is predictive of hormone therapy benefit in post-prostatectomy setting

A novel gene expression signature, PAM50, can predict which men will benefit from adding hormone therapy to radiation after radical prostatectomy, according to data from the phase 2 BALANCE trial (NRG GU006; NCT03371719) presented at the American Society for Radiation Oncology 67^th Annual Meeting in San Francisco, California.

Specifically, the study showed that patients with luminal B tumors, a PAM50 molecular subtype, derived greater clinical benefit from the addition of apalutamide to postoperative radiation in the postprostatectomy setting.

The results were presented by Daniel Spratt, MD, professor and chair of radiation oncology at University Hospitals Seidman Cancer Center and Case Western Reserve University School of Medicine in Cleveland, Ohio. Spratt explained that the novel luminal-basal classification was developed in 2015 based on work adapted from the breast cancer PAM50 assay.

“Hormone therapy remains the No. 1 driver of quality-of-life declines in men with this setting of disease,” he said. “[However,] we still had zero prospectively validated biomarkers that could help us predict which men benefit from hormone therapy.”

To that end, the investigators enrolled men who underwent radical prostatectomy with a prostate-specific antigen (PSA) level between 0.1 and 1.0 ng/mL with no evidence of metastatic disease. Gene expression profiling was applied to tissue samples from prostatectomy. Patients were then stratified by surgical margins (positive or negative), preradiotherapy PSA, and PAM50 molecular subtype. Patients were randomly assigned 1:1 to receive early secondary radiotherapy (SRT) with either 6 months of apalutamide or 6 months of placebo.

The primary end point was biochemical progression-free survival (bPFS). Secondary end points included metastasis-free survival (MFS), distant metastasis, salvage hormone therapy use, and toxicity.

Overall, the results aligned with the investigators’ hypothesis. In patients with luminal B subtype tumors, the addition of apalutamide to radiotherapy significantly improved outcomes, with a 5-year bPFS of 72% in the apalutamide arm compared with 54% in the placebo arm (HR, 0.45; 95% CI, 0.24 to 0.86; P = .0062). Conversely, in the nonluminal B subset, the addition of apalutamide showed no significant benefit, with 5-year bPFS rates around 70% in both groups (HR, 0.95; 95% CI, 0.65 to 1.41; P = .44).

Similar trends were observed for MFS. For patients with luminal B tumors, the 5-year MFS was 95% in the apalutamide group compared with 82% in the placebo group (HR, 0.27; 95% CI, 0.07 to 0.95; P = .029). For patients with nonluminal B tumors, MFS was similar, with 5-year MFS rates of 90% vs 89%, respectively (HR, 1.06; 95% CI, 0.41 to 2.78; P = .90).

Data also showed that the 6-month regimen of apalutamide with SRT was generally well tolerated. Overall, grade 3 or higher adverse events (AEs) were reported in 32% of patients in the apalutamide arm and 23% in the placebo arm. Specific grade 3 or higher AEs included rash (5% vs 0%, respectively), hypertension (13% vs 5%), cardiac disorders (0.7% vs 1.3%), and falls (0.7% vs 1.3%).

“This is the first prospectively validated predictive biomarker in prostate cancer,” concluded Spratt in a news release on the findings.² “It 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.”

Spratt also emphasized that a follow-up phase 3 trial is unlikely given the clear results from the BALANCE trial. “The magnitude of benefit—and the complete lack of benefit in some patients—makes it unlikely that we could ethically enroll patients in a follow-up trial. PAM50 could now be used in recurrent prostate cancer to support shared decision-making.”

REFERENCES

1. Spratt D. A double-blinded placebo-controlled biomarker stratified randomized trial of apalutamide (APA) and radiotherapy for recurrent prostate cancer (NRG GU006, BALANCE trial). Presented at: American Society of Radiation Oncology 67th Annual Meeting; September 27-October 1, 2025; San Francisco, CA. Abstract LBA04

2. First-of-its-kind genomic test predicts benefit from hormone therapy added to radiation for recurrent prostate cancer. News release. American Society for Radiation Oncology (ASTRO). September 26, 2025. Accessed September 29, 2025. https://www.newswise.com/articles/first-of-its-kind-genomic-test-predicts-benefit-from-hormone-therapy-added-to-radiation-for-recurrent-prostate-cancer