T suppression and recovery with AAP after early discontinuation of LHRH-A in high-risk localized (HRL), lymph node-positive (N+), or oligometastatic (OM) prostate cancer (PC).

Abstract

55 Background: Intensified androgen deprivation therapy (iADT) with the addition of abiraterone acetate + prednisone (AAP) to a luteinizing hormone releasing hormone agonist or antagonist (LHRH-A) is commonly used in conjunction with radiation therapy for HRL, N+ or OM hormone-sensitive PC. However, prolonged LHRH-A has been associated with delayed or incomplete testosterone (T) recovery after discontinuation (dc). As AAP monotherapy leads to castrate T, we investigated T kinetics with early discontinuation of LHRH-A when given in combination with AAP. Methods: The Dana-Farber/Harvard Cancer Center (DF/HCC) Oncology Data Retrieval System (OncDRS) was queried to identify patients (pts) planned to receive 18-24 mo of AAP for HRL, N+ or OM PC. Pts who previously received AAP for > 12 mo, with baseline T <150 ng/dl, received AAP for castration-resistant PC, received AAP >30 mo, or LHRH-A dc > 3 mo after AAP were excluded. T values at AAP end of treatment (EOT) and at each clinical follow up visit were tabulated to assess time to T recovery (TTR) to ≥150 ng/dl in pts with LHRH-A dc ≤3 mo, 3-12 mo and ≥12 mo prior to AAP EOT. Gray’s competing risk regression model was applied to assess the relationship between TTR and time between LHRH-A dc and AAP EOT. Results: The OncDRS query returned 350 pts, 105 meeting eligibility criteria with available T follow up after AAP EOT. 99 of 105 pts had available T at EOT, 99/99 (100%) with T < 20 ng/dl across the three groups. TTR was statistically significantly shorter for pts with LHRH-A dc ≥12 months prior to AAP EOT (median 3.2 mo [95% CI 1.8, 4.1]) compared to ≤3 mo prior to LHRH-A dc (median 20.0 mo [9.0, 27.6]) with all T recovery events within 6 months of EOT in the former group (Table). Conclusions: In this real-world cohort, early discontinuation of LHRH-A when given in combination with AAP led to ongoing T suppression while on AAP and shorter TTR after AAP EOT. This strategy warrants consideration when iADT is indicated but the patient seeks rapid and reliable T recovery after completion of treatment for the actual duration of T suppression desired. DF/HCC protocol # 23-322. TTR outcome summary. Timing of discontinuation of LHRH-A ≥ 12 months (N=13) 3 – 12 months (N=36) ≤ 3 months (N=56) No. T recovery events 10 26 26 No. competing events* 0 1 6 6-month cumulative TTR rate (95% CI) 82% (38%, 96%) 39% (23%, 55%) 15% (6.8%, 26%) 12-month cumulative TTR rate (95% CI) 82% (38%, 96%) 64% (46%, 78%) 39% (25%, 52%) Median (95%), month 3.2 (1.8, 4.1) 7.5 (3.7, 15.5) 20.0 (9.0, 27.6) Hazard ratio (95% CI) ref 0.40 (0.16, 1.02) 0.20 (0.08, 0.49) p-value ref 0.06 0.01 *New treatment without T recovery.