The phase II BALANCE trial (NRG GU006), presented at the American Society for Radiation Oncology (ASTRO) 67th Annual Meeting, evaluated whether genomic subtyping could identify which patients with recurrent prostate cancer after prostatectomy would benefit from adding apalutamide to salvage radiation therapy. The study used the PAM50 test, a gene expression tool originally developed for breast cancer and later adapted to prostate cancer, to classify tumors into molecular subtypes. The focus was on the luminal B subtype, which was hypothesized to be more responsive to hormonal therapy.

A total of 295 patients were enrolled in the trial, all with rising PSA levels between 0.1 and 1.0 ng/mL after prostatectomy but no evidence of nodal or distant metastasis. Patients were randomized to receive salvage radiation therapy combined with either placebo or apalutamide at a dose of 240 mg daily for six months. Randomization was stratified according to PAM50 subtype, luminal B or non–luminal B.

The results showed a meaningful difference based on molecular subtype. Among the 43% of patients with luminal B tumors, the addition of apalutamide led to a significant improvement in outcomes. Biochemical progression-free survival at five years was 72.4% with apalutamide compared to 53.9% with placebo. Metastasis-free survival at five years was 94.7% with apalutamide compared to 81.8% with placebo. By contrast, patients with non–luminal B tumors derived no clear benefit from apalutamide. In this group, biochemical progression-free survival was 70.2% with apalutamide and 71.1% with placebo, while metastasis-free survival was 89.9% and 89.3%, respectively.

The investigators concluded that PAM50 subtyping can help identify patients with recurrent prostate cancer most likely to benefit from adding hormonal therapy to salvage radiation.

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