Introduction
Relugolix is a first-in-class oral GnRH receptor antagonist that is administered once daily and was approved by the US Food and Drug Administration in 2020 for the treatment of adult patients with advanced prostate cancer. Findings from a phase 3 HERO study demonstrated that relugolix provides sustained testosterone suppression that is superior to that achieved with leuprolide.
Aim
The study aimed to analyze testosterone recovery in men from the HERO study who were not required to continue androgen deprivation therapy (ADT)
Patient Profile
Adult men (aged >18 yr) with histologically or cytologically confirmed adenocarcinoma of the prostate and were candidates for at least 1 yr of continuous ADT.
Methods
- The study included prespecified subset of men from the phase 3 HERO study
Study Outcomes
- Time to testosterone recovery (>280 ng/dl; >80% of baseline testosterone) during the 90-d recovery period
- Serum levels of prostate-specific antigen and pituitary hormones, and adverse events were measured
Results
Efficacy
- Men in the relugolix group recovered testosterone levels (>280 ng/dl) faster and at a higher rate (74/137) compared to those in the leuprolide group (2/47)
Figure 1: Cumulative incidence rate of testosterone recovery to >280 ng/dl at 90 d following drug discontinuation
- The median time to testosterone recovery was faster following relugolix treatment than with leuprolide acetate treatment
Figure 2: Time to testosterone recovery
- In post hoc analysis, men aged 65 years or younger experienced faster median testosterone recovery (61.5 days) compared to those older than 65 years (91.0 days)
- 90 days recovery rates for men with < 65 yr of age and men >65 yr of age were 78% and 47% for relugolix, respectively compared to 13% vs 0% for leuprolide acetate.
- Among men treated with relugolix, 93% achieved testosterone levels above castrate levels (≥50 ng/dl) within 90 days, compared to only 10% in the leuprolide group; additionally
- A greater proportion of men receiving relugolix (39%) reached 80% testosterone recovery from baseline compared to just 2.1% in the leuprolide cohort.
- 57% of those in the relugolix cohort with biochemical recurrence achieved testosterone levels greater than 280 ng/dL within a median recovery time of 83 days, whereas none in the leuprolide cohort reached this threshold.
- At the 90-day post-treatment follow-up, a significantly higher proportion of men in the relugolix cohort (42%) achieved at least 80% recovery of baseline testosterone levels compared to 0% in the leuprolide group
- There was no significant correlation between PSA levels and testosterone levels (p > 0.05).
Table 1: Prostate-specific antigen (PSA) ; follicle-stimulating hormone (FSH) and luteinizing hormone (LH) at 90-d visit
Measurement
Relugolix (n)
Leuprolide (n)
Median Value (Relugolix)
Median Value (Leuprolide)
PSA (ng/ml)
131
44
0.39
0.06
FSH (IU/L)
129
42
21.08
5.19
LH (IU/L)
129
44
9.70
0.35
Safety
- The incidence of AEs was generally similar between treatment cohorts during the recovery phase.
- Over 95% of men experienced at least one adverse event (AE) during treatment,
- 15% suffering from a grade 3 AE;
- 12% receiving relugolix had serious grade AEsvs 11% of those treated with leuprolide
- No deaths reported in either group
- Hot flashes were the most prevalent AE in both cohorts, affecting 63% of men treated with relugolix and 55% of those receiving leuprolide.
Conclusion
- Oral relugolix showed accelerated recovery of testosterone to normal levels following treatment discontinuation, when compared to leuprolide acetate.
- These findings may be significant for men being treated with androgen deprivation therapy and influence treatment decisions
Reference
Eur. Urol. Oncol. 2024:906-913
