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Castration resistance-free survival (CRFS) after 48-week treatment with relugolix was not significantly different compared with leuprolide in men with advanced prostate cancer and metastatic disease or in the overall modified intention-to-treat (mITT) population, according to study results presented at the 2021 American Urological Association Annual Meeting.
In the phase 3 HERO study (ClinicalTrials.gov Identifier: NCT03085095), investigators aimed to further characterize the efficacy profile of relugolix by assessing CRFS in the overall mITT population and a cohort of patients with metastatic disease. Relugolix had previously demonstrated superior suppression of testosterone to castrate levels vs leuprolide and was well tolerated in men with advanced prostate cancer.
The men were randomly assigned 2:1 to receive relugolix 120 mg orally once daily after 1 loading dose of 360 mg or leuprolide injections every 12 weeks for 48 weeks, with randomization stratified according to geographic region, presence or absence of metastatic disease, and age (≤75 and >75 years).
CRFS, which was not analyzed in the primary analysis, was assessed in an additional 144 men during 48 weeks of treatment. CRFS was defined as the time from the date of first dose to the date of confirmed prostate-specific antigen (PSA) progression according to Prostate Cancer Clinical Trials Working Group 3 while castrated or death due to any reason, whichever occurred earlier. Post-hoc multivariate Cox regression analysis was used to assess whether any baseline characteristics were associated with CRFS events.
A total of 1074 men (median age, 71.0 years) with advanced prostate cancer (relugolix: 717 patients; leuprolide: 357 patients) and 434 men with metastatic disease (relugolix: 290 patients; leuprolide: 144 patients) were included in the CRFS analysis (mITT population).
At 48 weeks, CRFS rates in the metastatic disease cohort were 74.3% (95% CI, 68.6-79.2) and 75.3% (95% CI, 66.7-81.9) in the relugolix and leuprolide groups, respectively (hazard ratio, 1.03 [0.68, 1.57]; P =.84). The findings were similar in the 2 groups in the overall mITT population.
All men had testosterone levels less than the castration threshold (<50 ng/dL) at the time of their CRFS event, except for 2 men in the leuprolide group who died without achieving castration. Participants’ last testosterone values on or before week 49 demonstrated maintenance of testosterone suppression after CRFS.
Stepwise multivariate Cox regression analysis showed the following risk factors were associated with a CRFS event (P <.05) after stepwise selection — PSA 20 or higher (P <.0001), metastatic disease at baseline (P <.0001), and former or current smoker (P =.0284).
Among adverse events (AEs) occurring in at least 5% of patients in either treatment group according to the preferred term for the metastatic disease cohort, 268 of 290 patients in the relugolix group reported at least 1 AE, and 129 of 144 in the leuprolide group had at least 1 AE.
“Overall, in the HERO study, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide in men with advanced prostate cancer,” stated the investigators. “These results suggest that low testosterone levels on androgen deprivation therapy are not a driver of early castration resistance.”
Disclosure: This research was funded by Myovant Sciences GmBH, in collaboration with Pfizer.
Saad F, George DJ, Cookson MS, et al. Relugolix vs leuprolide effects on castration resistance-free survival from the phase 3 HERO study in men with advanced prostate cancer. Presented at: AUA2021 Virtual Experience held September 10-13, 2021. MP24-07.