Phase III HERO Trial Finds Relugolix to be Superior to Leuprolide in Prostate Cancer

Results from the phase III HERO trial, presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting, indicated that relugolix (Relumina) demonstrated superiority over leuprolide (Lupron) in sustained testosterone (T)-suppression through 48 weeks, fast T-recovery after discontinuation, and a 50% reduction in major adverse cardiovascular events (MACE) in patients with advanced prostate cancer. 

Moreover, relugolix achieved castration as early as day 4, suggesting the potential for this agent to become a new standard for T-suppression in this patient population.

“Relugolix is a novel, oral GnRH receptor antagonist that achieves both LH and FSH suppression to its direct inhibitory effect on the pituitary GnRH receptors,” Neal D. Shore, FACS, MD, of NAME NAME, said in a press release. “This direct inhibition does not result in a testosterone surge.”

The 48-week, global, pivotal phase III trial randomized 934 patients with androgen-sensitive advanced prostate cancer in a 2:1 ratio to receive either 120 mg of relugolix orally once daily after a 1-time 360 mg loading dose (n = 624) or a 3-month depot injection of leuprolide acetate (n = 310). Testosterone recovery was also evaluated in a subset of 184 patients.

The primary endpoint was to achieve and maintain serum T-suppression to castrate levels (< 50 ng/dL) through 48 weeks. Key secondary endpoints included castration rates at day 4 and day 15, profound castration (< 20 ng/dL) rates at days 4 and 15, PSA response rate at day 15, and FSH levels at week 24. 

Overall, 96.7% (95% CI, 94.9%-97.9%) of men treated with relugolix achieved and maintained castration through 48 weeks compared to 88.8% on leuprolide. Notably, the difference of 7.9% (95% CI, 4.1%-11.8%) demonstrated non-inferiority (margin -10%) and superiority (P < 0.0001) of relugolix to leuprolide. All key secondary endpoints also demonstrated superiority over leuprolide (P < 0.0001).

In the subset of patients evaluated for testosterone recovery, median T-levels were 270.76 ng/dL in the relugolix group compared to 12.26 ng/dL in the leuprolide group 90 days after discontinuation of therapy. 

In a prespecified analysis, the incidence of MACE was found to be lower in the relugolix group than in the leuprolide group (2.9% vs 6.2%, respectively). Otherwise, the safety and tolerability profiles of the 2 agents were generally similar. 

Adverse events (AEs) reported for >10% of patients treated with relugolix or leuprolide were hot flush (54.3% vs 51.6%, respectively), fatigue (21.5% vs 18.5%), constipation (12.2% vs 9.7%), diarrhea (12.2% vs 6.8%), arthralgia (12.1% vs 9.1%), and hypertension (7.9% vs 11.7%). Notably, AEs of diarrhea were of grade 1 or 2 and did not result in study discontinuation.

“Relugolix once daily was well tolerated with an adverse event profile consistent with T-suppression,” Shore said. “Most notably, the risk of major adverse cardiovascular events was 54% lower in the relugolix group compared to leuprolide.”

“Relugolix is a novel, oral GnRH antagonist that has the potential to become a new standard for ADT in advanced prostate cancer,” Shore concluded.

Reference:

Shore ND, George DJ, Saad F, et al. HERO phase III trial: Results comparing relugolix, an oral GnRH receptor antagonist versus leuprolide acetate for advanced prostate cancer. Presented at: 2020 ASCO Virtual Scientific Program. Abstract 5602.