A clinical trial has validated the first predictive biomarker to guide the use of hormonal therapy in prostate cancer, according to research presented at the American Society for Radiation Oncology (ASTRO) meeting in San Francisco. In a phase II trial involving 295 patients undergoing salvage radiotherapy, those with a molecular prostate tumor subtype known as luminal B had improved biochemical progression-free survival when they received apalutamide compared to non-luminal B patients, noted principal investigator Daniel Spratt, MD, of Case Western Reserve University in Cleveland.
“[Hormone therapy] has been shown in localized prostate cancer to improve outcomes, but we still have zero prospectively validated biomarkers that can help us predict which men benefit from hormone therapy,” Spratt said in a September 29 media briefing held by ASTRO.
For patients with rising PSA levels after undergoing prostatectomy, radiation therapy is the standard treatment and has been shown to improve survival. Hormone therapy is commonly added to radiation in this setting to block or reduce testosterone, a hormone that fuels prostate cancer growth, Spratt explained.
Yet currently there are no prospectively validated predictive biomarkers to guide use of hormonal therapy in these patients. Thus, Spratt and colleagues conducted a phase II biomarker stratified randomized trial to test whether patients with transcriptionally defined molecular subtypes would differentially benefit from the hormone therapy apalutamide.
Between April 2018 and February 2020, 295 patients with recurrent prostate cancer and no signs of metastasis were enrolled at cancer centers across the U.S. All patients had undergone prostatectomy and were experiencing a rising PSA (86% with entry PSA of <0.5 ng/mL). They were randomized to receive a standard course of radiation therapy with six months of either apalutamide (a second-generation anti-androgen therapy) or placebo.
Using a genetic test called PAM50, patients were grouped as luminal B (n = 127) or non-luminal B (n = 168). Luminal B tumors are a subtype that grows more quickly, Spratt noted. The primary endpoint was biochemical progression-free survival, a measure of whether the cancer returned based on PSA levels, recurrence, metastasis or death. The median follow-up was five years.
According to the results, patients with luminal B tumors saw a significant benefit from hormone therapy. Their five-year biochemical progression-free survival was 72.4% with apalutamide, compared to 53.9% with placebo (p = 0.0062). In contrast, those with non-luminal B tumors saw no benefit, with nearly identical five-year biochemical control between the hormone and placebo arms (70.2% vs. 71.1%, p = 0.44).
In addition, a similar pattern emerged for metastasis-free survival. Among luminal B patients, five-year survival without metastasis was 94.7% with hormone therapy and 81.8% with placebo (p = 0.029). Conversely, no difference was seen in the non-luminal B group (89.9% versus 89.3%, p = 0.90).
“We demonstrate that patients with luminal B tumors drive clinically meaningful benefits from the addition of apalutamide to secondary radiotherapy, and these benefits were not observed in non-luminal B patients,” Spratt said.
Ultimately, Spratt said the results were so definitive that a phase III trial is unlikely. Moreover, the trial validated the clinical use of the PAM50 genetic test, he added.
“PAM50 now represents actually the first and only prospectively validated predictive biomarker to guide hormone therapy,” Spratt said.