Relugolix leads to rapid, sustained profound testosterone suppression in advanced PCa

Use of the oral non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix led to faster and greater sustained profound testosterone suppression than leuprolide in men with advanced prostate cancer, according to results of the phase III HERO study presented at EAU 2022.

The population comprised 934 men with advanced prostate cancer who were randomized 2:1 to receive oral relugolix (single oral loading dose of 360 mg on day 1 followed by 120 mg QD; n=622) or subcutaneous leuprolide (22.5 mg* every 12 weeks; n=308) for 48 weeks.

Previously published results showed greater sustained castration rates with relugolix than leuprolide at 48 weeks (testosterone suppression to <50 ng/dL: 96.7 percent vs 88.8 percent; p_superiority<0.001) and greater profound castration levels (<20 ng/dL) at day 15 (78.4 percent vs 1.0 percent; p<0.0001). [N Engl J Med 2020;382:2187-2196]

In the present analysis, time to profound castration (time from the date of first dose to the date of initial testosterone suppression to <20 ng/dL) was shorter among patients who received relugolix than leuprolide (median 15 vs 29 days). [EAU 2022, abstract A0514]

At 48 weeks, more patients who received relugolix than leuprolide experienced sustained profound castration (81.6 percent vs 68.6 percent).

“Profound castration rates were sustained and higher for the relugolix group compared with the leuprolide group at all measured timepoints,” presented study author Professor Bertrand Tombal from the Université Catholique de Louvain, Institut de Recherche Clinique, Brussels, Belgium.

The profound castration rates for patients receiving relugolix vs leuprolide at day 4, 8, 22, and 29 were 6.9 percent vs 0 percent, 27.1 percent vs 0 percent, 91.1 percent vs 10.5 percent, and 95.3 percent vs 56.9 percent, respectively.

The rates of adverse events (AEs) were comparable between the relugolix and leuprolide groups (92.9 percent vs 93.5 percent), as were rates of grade ≥3 AEs (18.0 percent vs 20.5 percent). The most common AEs (>10 percent) in the relugolix vs leuprolide groups were hot flush (54.3 percent vs 51.6 percent) and fatigue (21.5 percent vs 24.4 percent). The cases of diarrhoea (12.2 percent vs 6.8 percent) and constipation (12.2 percent vs 9.7 percent) were grade 1–2 in severity.

“Testosterone levels <20 ng/dL are associated with improved overall and cancer-specific survival outcomes,” said Tombal. These levels can be achieved with both medical and surgical castration, he noted.

“Relugolix … demonstrated more rapid and higher sustained profound testosterone suppression compared with leuprolide in the phase III HERO study at all measured timepoints,” he concluded.