Here, we conducted a study to assess the safety and efficacy of relugolix combined with abiraterone acetate or apalutamide.4 We presented results from this ongoing, two-part, Phase I, 52-week, open-label cohort study in patients with advanced prostate cancer (NCT04666129), which evaluated relugolix in combination with abiraterone acetate and a corticosteroid (prednisone or methylprednisolone) in Part 1, and relugolix combined with apalutamide in Part 2. Eligible patients had either metastatic castration-sensitive prostate cancer (mCSPC; both parts), nonmetastatic castration-resistant prostate cancer (Part 2), or metastatic castration-resistant prostate cancer (Part 1). Patients receiving leuprolide acetate or degarelix at baseline were transitioned to relugolix 120 mg once daily in Part 1 and relugolix 240 mg once daily in Part 2, after a single loading dose of 360 mg. Combining relugolix with apalutamide in Part 2 necessitated the doubling of relugolix dosing as apalutamide, a P-glycoprotein and strong CYP3A inducer, has the potential to reduce concentrations of relugolix in vivo. This interim analysis reported safety parameters, and drug and testosterone concentrations in patients who completed ≥12 weeks or who terminated early, with at least one administration of combination treatment.
In Part 1, 15 patients received relugolix in combination with abiraterone acetate for a median duration of 281 days; whereas in Part 2, 10 patients received relugolix in combination with apalutamide for a median duration of 180 days. The mean age was 72.3 years in Part 1 and 68.1 years in Part 2. Overall, 86.7% of patients in Part 1 and 100% of patients in Part 2 had mCSPC.
Among the 15 patients enrolled in Part 1, 79 nonserious, adverse events (AEs) were reported, most being of grade 1 or 2. Of these nonserious AEs, 18, 21, and four AEs were considered possibly or probably related to relugolix, abiraterone acetate, and corticosteroid, respectively. A single instance of hospitalization due to a left femur fraction was the only serious, grade 3 AE reported, considered unrelated to the study treatment. The most frequently reported AEs occurring in ≥10% of patients included pain in extremities, increase in alanine aminotransferase (ALT), anemia, back pain, constipation, hypertension, memory impairment, rash, and vomiting.
Among the 10 patients enrolled in Part 2, 28 nonserious AEs were reported; most were grade 1 or 2, while 2 AEs were considered severe (grade 3–4). Of these nonserious AEs, 11 and 12 AEs were considered possibly or probably related to relugolix and apalutamide, respectively. A single instance of a neuroendocrine tumor was considered a serious AE, unrelated to the study treatment. The most frequently reported AEs occurring in ≥10% of patients included pain in extremities, increased ALT, anemia, and vomiting. No shifts in clinical laboratory and electrocardiogram parameters or vital signs were observed, nor were there any changes that could be related to the transition from prior ADT to relugolix, in either part of the study. Testosterone serum concentrations remained below castration levels after the transition to relugolix until the end of the primary study treatment period in both study parts.
Combination treatment with relugolix had a tolerable safety profile and maintained serum testosterone below castration levels in patients with advanced prostate cancer. The results of this interim analysis support the use of relugolix as ADT in combination with abiraterone acetate or apalutamide.
Written by: Jose De La Cerda, MD, Urology San Antonio, San Antonio, TX
References:
- Lowrance W, Dreicer R, Jarrard DF, et al. Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023). J Urol. 2023;209(6):1082–1090.
- Parker C, Castro E, Fizazi K, et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(9):1119–1134.
- Shore ND, Saad F, Cookson MS, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020;382(23):2187–2196.
- De La Cerda J, Dunshee C, Gervasi L, et al. A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer. Target Oncol. 2023;18(3):383-390.
Dr. De La Cerda reports consulting or advisory roles with Dendreon, Myriad Pharmaceuticals, and Pfizer/Astellas. This study was sponsored by Pfizer Inc., in collaboration with Sumitomo Pharma Switzerland GmbH. Medical writing and editorial assistance for this commentary were provided by Katerina Pipili, PhD, and Rosie Henderson, both of Onyx (a division of Prime, London), funded by Pfizer Inc., in collaboration with Sumitomo Pharma Switzerland GmbH.
Read the Abstract