Maintenance of castration with concomitant relugolix and apalutamide (Apa) in patients with high-risk localized prostate cancer (HR-LPC): 1 year update.

Abstract

e17094 Background: Androgen deprivation therapy (ADT) is a mainstay in the management of prostate cancer (PC). We assessed the efficacy of achieving and maintaining castrate testosterone (T) levels when combining relugolix, an oral gonadotropin-releasing hormone antagonist, concomitantly with Apa, an androgen receptor inhibitor. The single-arm, open-label, multicenter, phase 2 Apa-RP study evaluates the biochemical recurrence-free rate in patients with HR-LPC following radical prostatectomy (RP) who received 12 months of adjuvant Apa and ADT (main study). A substudy was added to assess whether the approved maintenance dose of relugolix with concomitant Apa maintained castration. Study results of the 28-day coadministration of relugolix + Apa showed that all evaluable patients achieved and maintained castration at standard relugolix dose and were transitioned into the main study (Brown et al. Target Oncol. 2022). Herein, we report longer term data of T levels and safety findings in the substudy patients who received relugolix + Apa for 1 year. Methods: Patients (n = 12) with HR-LPC (PSA ≥20 ng/mL or Gleason score ≥8) received a loading dose of relugolix (360 mg) at substudy initiation (Day -14) followed by the standard, approved relugolix dose (120 mg/d) for 13 days. Starting on Day 1, patients received relugolix + Apa (240 mg/d) for 28 days, with substudy completion on Day 28. These patients transitioned to the main study and received relugolix + Apa for a total of 1 year. T levels (castrate level defined as < 50 ng/dL) were measured at baseline (Day -14), Day 1, Day 28, and then every 3 months. Results: Of the 12 patients who continued onto the main study, 1 withdrew and another was noncompliant with therapy and subsequently withdrew but maintained castration while on therapy. Of the 10 patients who successfully completed therapy, 100% maintained castration during 1 year of concomitant therapy with relugolix + Apa . No patient required dose modification of relugolix. Median T level was 10.0 ng/dL after 1 year of treatment. One month after treatment discontinuation, 8/10 (80%) patients saw recovery of their T (T ≥50 ng/dL). Treatment-emergent adverse events (TEAEs) occurred in all 12 patients (100%). TEAEs were consistent with known safety profiles for each drug administered separately. Conclusions: During the 12 months of concomitant relugolix + Apa administration, all patients who completed therapy maintained castrate T levels without relugolix dose modification. All but 2 patients had T recovery within 30 days of therapy discontinuation. These data support long-term T suppression with relugolix + Apa at standard doses. Subsequent T levels will be reported upon final analysis of the main study. Clinical trial information: NCT04523207 .