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

Abstract

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. The aim of this study was to evaluate whether the approved standard maintenance dose of relugolix in combination with apalutamide sustains castrate testosterone levels (< 50ng/dL). Twelve patients with HR-LPC who met all the main study criteria were included in the substudy. Patients received relugolix monotherapy for 2weeks (loading dose [360mg] at Day - 14 then 120mg/day daily until Day - 1), then daily relugolix (120mg) with apalutamide (240mg) from Day 1 to Day 28. Endpoints were rate of maintained castration (testosterone < 50ng/dL) through Day 28 (primary) and safety (secondary). All 12 patients received relugolix and apalutamide and achieved castrate testosterone levels after 2-week relugolix monotherapy (median testosterone 348.5ng/dL and 8.7ng/dL at Days - 14 and - 1). All 11 patients who had testosterone measured at Day 28 maintained castrate testosterone (median 10.0ng/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. Relugolix administered at approved standard doses concurrently with apalutamide was effective in maintaining castrate testosterone levels in HR-LPC without new safety signals. NCT04523207, 21 August 2020.