Relugolix effective, well tolerated in Asian men with advanced prostate cancer

In the subgroup analysis of the HERO trial, the first-in-class oral, highly selective, GnRH* antagonist relugolix was effective and well tolerated in Asian men with advanced prostate cancer.

“In the [overall analysis of this] global phase III study, relugolix demonstrated superior sustained suppression of testosterone to castrate levels from day 29 through week 48 compared with leuprolide in men with advanced prostate cancer,” said Professor Dingwei Ye from the Fudan University Shanghai Cancer Center, Shanghai, China, during his presentation at ESMO Asia 2022.

“In this subgroup analysis, [our results were] consistent with that seen in the overall population … [There were] sustained profound castration rates through week 48,” Ye continued.

The overall cohort comprised 934 men who were randomized 2:1 to receive either relugolix (120 mg QD after a single loading dose of 360 mg) or leuprolide injections for 48 weeks. Leuprolide dose was 22.5 mg, except in Japan and greater China, which used the 11.25-mg dose. The current analysis included a subgroup of Asian men (from greater China, Japan, South Korea) from the overall HERO cohort (n=297; median age 72 years). [ESMO Asia 2022, abstract 161MO]

The rates of sustained testosterone suppression to castrate levels (<50 ng/dL) were generally higher with relugolix compared with leuprolide, be it in the Asian cohort (97 percent vs 89 percent) or in the individual countries (98 percent vs 93 percent [for both China and Japan] and 95 percent vs 81 percent [South Korea]).

“Of note, the countries that utilized the 11.25-mg dose of leuprolide did not have lower rates,” Ye said.

Compared with those on leuprolide, more patients on relugolix had a prostate specific antigen response on day 15 followed with confirmation on day 29 (85 percent vs 34 percent).

As to the other select key secondary endpoints, almost all men on relugolix (98 percent) had a cumulative probability of T suppression to <50 ng/dL on day 15, as opposed to only 9 percent in the leuprolide arm. None of the men on leuprolide had cumulative probabilities of T suppression to <50 ng/dL (day 4) and profound T suppression to <20 ng/dL (day 15); in the relugolix arm, the corresponding rates of participants achieving these two endpoints were 51 percent and 81 percent, respectively.

Safety-wise, there were similar fractions of participants between the relugolix and leuprolide arms reporting grade 3/4 adverse events (18 percent vs 16 percent). This also corresponded with what has been observed in the overall cohort (19 percent vs 20 percent).

Considering the adverse effects (ie, injection-related issues, delayed effects, symptom flares) associated with treatment alternatives for medical castration in prostate cancer (LHRH** agonists, degarelix), these findings underpin the potential of the first oral GnRH antagonist for the treatment of men with advanced prostate cancer. [Urology 2010;75:642-647, Int J Urol 2012;19:594-601; Cancer Med 2019;8:5891-5902]