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Published on: March 6, 2018
Safety and Tolerability of Relugolix in Combination with Abiraterone or Apalutamide for Treatment of Patients with
Jose De La Cerda1, Laurence Belkoff2, Kevin D Courtney3
1Urology San Antonio, 3327 Research Plaza Suite 403, San Antonio, TX, 78235, USA. Jose.DeLaCerda@urologysa.com.
Background:
The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix is the only oral androgen deprivation therapy (ADT) indicated for advanced prostate cancer (aPC). Combining ADT with androgen receptor signaling inhibitors (ARSIs) has shown improved clinical outcomes.
Objective:
To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of relugolix in combination with ARSIs in patients with aPC.
Methods:
In this 52-week, open-label study, patients received relugolix (120 mg once daily) with abiraterone (1,000 mg once daily) and corticosteroid (Part 1) or relugolix (240 mg once daily) with apalutamide (240 mg once daily) (Part 2). Metastatic castration-sensitive patients were eligible for both parts, whereas castration-resistant patients were eligible for Part 1 if metastatic and Part 2 if non-metastatic. Adverse events and other safety data were evaluated over 52 weeks, while pharmacodynamic and pharmacokinetic (Part 2 only) data were assessed over 12 weeks. Medication adherence to relugolix was measured by pill count.
Results:
Of 48 patients, 21 completed Part 1 and 20 completed Part 2. Most adverse events were grade 1 or 2, with hypertension (Part 1) and rash (Part 2) being most common. Mean testosterone concentrations remained below castrate level. Median prostate-specific antigen concentration was 0.04 ng/mL at week 12 in both parts. Concentrations of relugolix, apalutamide, and N-desmethyl-apalutamide were stable over 12 weeks similar to previous data. Relugolix adherence rates were > 97% in both parts.
Conclusions:
The safety/tolerability profile of both combination therapies was consistent with those of the individual drugs. These findings support using relugolix in combination with abiraterone or apalutamide as treatment of aPC.
Clinical Trial Registration:
ClinicalTrials.gov identifier NCT04666129.
Insights
This study shows that combining relugolix with abiraterone or apalutamide is safe and effective for advanced prostate cancer (aPC). Both combinations effectively lower testosterone and prostate-specific antigen levels, supporting their use in aPC treatment.
Area of Science:
- Oncology
- Pharmacology
- Urology
Background:
- Relugolix is an oral GnRH receptor antagonist and the sole oral androgen deprivation therapy (ADT) for advanced prostate cancer (aPC).
- Combining ADT with androgen receptor signaling inhibitors (ARSIs) improves clinical outcomes in aPC.
- This study evaluates novel combination therapies for aPC management.
Purpose of the Study:
- To assess the safety and tolerability of relugolix combined with ARSIs in aPC patients.
- To evaluate the pharmacokinetics and pharmacodynamics of these combination therapies.
- To determine medication adherence in patients receiving relugolix-based regimens.
Main Methods:
- A 52-week, open-label study involving patients with advanced prostate cancer.
- Part 1: Relugolix (120 mg daily) + abiraterone (1,000 mg daily) + corticosteroid.
- Part 2: Relugolix (240 mg daily) + apalutamide (240 mg daily).
Main Results:
- Most adverse events were low-grade (1 or 2), with hypertension and rash being most frequent.
- Mean testosterone levels remained below castrate levels, and median PSA was 0.04 ng/mL at week 12.
- High medication adherence (>97%) and stable drug concentrations were observed.
Conclusions:
- Combination therapies of relugolix with abiraterone or apalutamide demonstrate a safety and tolerability profile consistent with individual drug profiles.
- These findings support the use of relugolix in combination with abiraterone or apalutamide for treating advanced prostate cancer.
- The study provides evidence for effective androgen deprivation and tumor marker control with these novel oral combinations.
