Coadministration of Apalutamide and Relugolix in Patients with Localized Prostate Cancer at High Risk for Metastases

BACKGROUND: The single-arm, open-label, multicenter, phase II Apa-RP study evaluates the biochemical recurrence (confirmed prostate-specific antigen [PSA] > 0.2 ng/mL)-free rate in patients with high-risk localized prostate cancer (HR-LPC) after radical prostatectomy following adjuvant apalutamide and androgen-deprivation therapy. In this substudy, relugolix, an oral gonadotropin-releasing hormone antagonist, was evaluated in combination with apalutamide. OBJECTIVE: The aim of this study was to evaluate whether the approved standard maintenance dose of relugolix in combination with apalutamide sustains castrate testosterone levels (< 50 ng/dL). PATIENTS AND METHODS: Twelve patients with HR-LPC who met all the main study criteria were included in the substudy. Patients received relugolix monotherapy for 2 weeks (loading dose [360 mg] at Day − 14 then 120 mg/day daily until Day − 1), then daily relugolix (120 mg) with apalutamide (240 mg) from Day 1 to Day 28. Endpoints were rate of maintained castration (testosterone < 50 ng/dL) through Day 28 (primary) and safety (secondary). RESULTS: All 12 patients received relugolix and apalutamide and achieved castrate testosterone levels after 2-week relugolix monotherapy (median testosterone 348.5 ng/dL and 8.7 ng/dL at Days − 14 and − 1). All 11 patients who had testosterone measured at Day 28 maintained castrate testosterone (median 10.0 ng/dL) without relugolix dose adjustment. Treatment-emergent adverse events (TEAEs) occurred in nine patients during relugolix monotherapy and in eight patients during relugolix + apalutamide coadministration. Hot flush was the most common TEAE reported, in six and four patients, respectively. CONCLUSIONS: Relugolix administered at approved standard doses concurrently with apalutamide was effective in maintaining castrate testosterone levels in HR-LPC without new safety signals. TRIAL REGISTRATION NUMBER AND DATE: NCT04523207, 21 August 2020. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11523-022-00932-8.