Impact of Age on Efficacy and Safety of Relugolix: A Subgroup Analysis from the Randomized, Phase 3 HERO Study versus Leuprolide in Men with Advanced Prostate Cancer

Background: As demonstrated in the phase 3 HERO study (NCT03085095), the oral GnRH receptor antagonist relugolix (REL) sustained testosterone (T) suppression superior to that of leuprolide (LEUP) and a comparative 54% decrease in risk of major adverse cardiovascular events. REL was recently approved for the treatment of men with advanced prostate cancer (APC).

Objective: To further characterize the impact of age on the use of REL in APC from the HERO study.

Methods: HERO was a randomized, open-label, parallelgroup study evaluating REL in men with APC. Overall, 934 men with APC underwent 2:1 randomization to receive REL 120 mg orally once daily after a single loading dose of 360 mg or LEUP 3-month injections for 48 weeks. Subgroups analyzed by age were <65 years or ≥65 years and ≤75 years or >75 years. Assessments analyzed included sustained T suppression to castrate levels (<50 ng/dL) from day 29 through 48 weeks, early and profound (<20 ng/dL) castration rates, prostate-specific antigen levels, and safety. T recovery (≥280 ng/dL) was evaluated in 184 men who enrolled in the T recovery substudy.

Results: Of the 930 men (REL: 622; LEUP: 308) who received the study drug, 173 (18.6%) were <65 years and 757 (81.4%) were ≥65 years of age, while 664 (71.4%) were ≤75 years and 266 (28.6%) were >75 years of age. Across all age subgroups, point estimates for sustained castration rates through 48 weeks for REL patients were consistent with the overall estimate of REL sustained castration rates observed in the overall population. Differences in sustained castrations rates at week 48 between REL and LEUP groups were 6.8% (95% CI, -4.3%-17.9%) in <65 years, 8.2% (95% CI, 4.2%-12.2%) in ≥65 years, 6.3% (95% CI, 1.7%-10.8%) in ≤75 years, and 12.1% (95% CI, 5.0%-19.2%) in >75 years. The likelihood of T recovery at 90 days after completion of treatment was higher in the REL group versus the LEUP group in all age subgroups: <65 (79.1% vs 16.7%), ≥65 (48.6% vs 0%), ≤75 (60.0% vs 4.0%), and >75 years (40.7% vs 0%). No clinically relevant differences were noted in the incidence or types of adverse events within treatment groups in all the age subgroups analyzed.

Conclusions: In this subgroup analysis of the HERO study, REL was effective regardless of age, and the benefit/risk profile remained favorable for REL compared with LEUP, consistent with the overall population. T recovery was higher in the REL group than in the LEUP group for all age subgroups analyzed, with higher rates of recovery in younger men.

Sponsorship: Myovant Sciences GmbH, in collaboration with Pfizer, Inc.

© 2021 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2021 ASCO Annual Meeting. All rights reserved.