Relugolix Shows Safety, Efficacy With and Without Concomitant Prostate Cancer Therapy

Treatment with relugolix and concomitant therapies for advanced prostate cancer showed similar safety and efficacy to relugolix alone in a study published in Clinical Genitourinary Cancer.

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor agonist that was approved by the FDA for use in advanced prostate cancer in 2020. The approval was based on data from the randomized, open-label, phase 3 HERO trial of relugolix vs leuprolide for testosterone suppression in androgen-sensitive advanced prostate cancer.

The current study, which analyzed clinical safety, efficacy, and drug concentration data from the HERO trial, aimed to determine whether using relugolix with enzalutamide or docetaxel had an impact on the agent’s efficacy or safety.

“Given the importance of combination therapy in the management of men with advanced prostate cancer, an understanding of potential synergies and drug-drug interactions for key therapies is imperative,” the authors wrote.

A total of 934 patients were randomized 2:1 to receive either daily oral relugolix or leuprolide injections once every 12 weeks in the HERO study, in which relugolix demonstrated superiority to leuprolide. Patients were able to receive either enzalutamide or docetaxel beginning 2 months after study initiation if their prostate-specific antigen levels increased during treatment with relugolix or leuprolide.

Of the patients included in the trial, 125 (13.4%) received either concomitant enzalutamide or docetaxel, which have potential to impact testosterone levels. The study included a primary analysis population and a final analysis population, which included additional patients with metastatic disease who were enrolled for the castration resistance-free analysis.

In the relugolix and leuprolide groups, enzalutamide was the most frequently used concomitant therapy (2.7% and 1.9% of patients, respectively). Docetaxel was used to treat 1.3% and 1.6%, respectively. The mean duration of enzalutamide was 12.9 weeks in the relugolix group and 14 weeks in the leuprolide group in the final analysis population.

Concomitant therapy did not impact testosterone levels, and castration rates were similar with or without concomitant therapy in the relugolix and leuprolide treatment groups. There were no significant differences in terms of adverse events in those who received concomitant therapy vs monotherapy in either treatment subgroup relative to the rest of the HERO trial population.

Relugolix trough concentrations and testosterone concentrations were similar in patients treated with relugolix monotherapy and those in the concomitant enzalutamide group, “suggesting that any induction or inhibition properties of enzalutamide on relugolix metabolism result in a neutral net effect on relugolix exposure and testosterone suppression,” the authors wrote.

The study was limited by its small size, and the data analyzed were limited to concomitant enzalutamide and docetaxel. The authors noted that an ongoing study will provide insight into relugolix in combination with abiraterone and apalutamide, and a previous study showed that relugolix plus apalutamide maintained castrate testosterone levels effectively in high-risk localized prostate cancer after radical prostatectomy for nonmetastatic disease.

Overall, the findings suggest that concomitant enzalutamide or docetaxel did not affecty testosterone suppression compared with patients given relugolix alone.

“Standard-of-care use of concomitant relugolix used in combination with these agents is supported by these data,” the authors concluded. “Further prospective studies are justified combining relugolix with other systemic treatment options for advanced prostate cancer.”

Reference

George DJ, Saad F, Cookson MS, et al. Impact of concomitant prostate cancer medications on efficacy and safety of relugolix vs leuprolide in men with advanced prostate cancer. Clin Genitourin Cancer. Published online March 23, 2023. 10.1016/j.clgc.2023.03.009