Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer The New England Journal of Medicine

[Balsam01]

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•The authors of this randomized phase 3 trial compared the oral gonadotropin-releasing hormone antagonist, relugolix, with leuprolide in over 900 men with advanced prostate cancer. Sustained castrate-level testosterone suppression (primary endpoint) was superior with relugolix (97% vs 89% through 48 weeks). In addition, cardiovascular event risk was lower with relugolix.

•The use of relugolix was associated with rapid and durable suppression of testosterone levels with a lower risk of major adverse cardiovascular events compared with leuprolide.

– Paul J. Hampel, MD

BACKGROUND

Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known.

METHODS

In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients.

RESULTS

A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88).

CONCLUSIONS

In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).

Article Citation

The New England Journal of Medicine

Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer

N. Engl. J. Med 2020 Jun 04;382(23)2187-2196, ND Shore, F Saad, MS Cookson, DJ George, DR Saltzstein, R Tutrone, H Akaza, A Bossi, DF van Veenhuyzen, B Selby, X Fan, V Kang, J Walling, B Tombal

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[LearnAll]

Thanks for posting this. Amazing results. I see Lupron injections era coming to end soon. This will give patients more control over their treatment. A welcome development.

[ragnar2020]

Greetings Y'all,

I saw Dr. Shore's presentation on GrandRounds, and it was impressive. For myself, Relugolix may be the answer if and when I encounter BCR. I'm approaching the ninth month post-RARP and will have an uPSA test the end of June. My previous non-ultra-sensitive PSA (mistake) was "undetechable," so I'll be interested to see my results now.

My PCa disease is Gleason 9/10 Cat. 5, pT3a NO with EPE. My pre-op PSA was <5.0.

My complication is that I have extensive coronary artery disease (CAD) with five internal heart blockages. I opted not to have by-pass surgery after multiple opinions, and instead changed my nutritional program to plant based and eliminated all animal based fat intake. I won't bore you with those results that have occurred during the past five years, but many gastric ailments disappeared along with fifty pounds and all the SEs from the CAD. Now, I have what is known in the CAD care world as "stable arterial plaque with extensive collaterals naturally by-passing internal blockages."

Then PCa was detected in the spring/summer of 2019. I was diagnosed with a DRE by my PCP and then a urologist. I chose to have a RARP at MGH in Boston, and the operation went well as did my post-op recovery. Because of the CAD and a clogged vascular system that services my Johnson, when possible permanent impotence was discussed with my surgeon, I explained that my QOL and LTS were my goals. I'd had an active pre-Medicare sex life, so if LTS and QOL was the trade off for the retirement of my Johnson, that was okay.

Fast forward to now. When the BCR occurs, I'd like to avoid radiation. But research indicates that most ADT brings with it possible cardiac complications. Apparently, the vascular plaque that has stabilized along the walls of my vascular system after the elimination of animal proteins and their resultant inflammation can be disrupted by many of the ADT drugs. Small pieces of vascular plaque can dislodge that often lead to MACE. I'd prefer to use ADT as a BCR treatment instead of systemic radiation, so hopefully Relugolix will offer me an option instead of rolling the dice between a major MACE event or treating the PCa recurrence with other ADT drugs.

[Dd7757]

Is there any indication of the side effect profile of Relgolix ?