Below is the abstract for a poster at the forthcoming ASCO meeting. They followed 33 mcrPca patients whose androgen blocking therapy had failed and looked at changes in DNA and androgen receptor expressions under a high dose testosterone regime - both BAT style and continuous gel. Interestingly, they had patients with bone mets. High T decreased altered AR expression in 100% of patients that had altered ARs at the start. Both BAT and gel were effective and the overall result seems to indicate that resensitization to androgen blockers is possible. Small sample, no longer term follow up but interesting.
abstracts.asco.org/239/Abst...
"AR changes in circulating-tumor DNA (ctDNA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with high-dose testosterone.
Sub-category:
Advanced Disease
Category:
Genitourinary (Prostate) Cancer
Meeting:
2019 ASCO Annual Meeting
Abstract No:
5058
Poster Board Number:
Poster Session (Board #170)
Citation:
J Clin Oncol 37, 2019 (suppl; abstr 5058)
Author(s): Marcus W. Moses, Elisa Ledet, Charlotte Manogue, Patrick Cotogno, Brian E. Lewis, A. Oliver Sartor, Pedro C. Barata, Jodi Lyn Layton; Tulane University, New Orleans, LA; Tulane University Cancer Center, New Orleans, LA; Office of Clinical Research, Tulane Cancer Center, New Orleans, LA; Tulane University School of Medicine, New Orleans, LA; Tulane Medical School, New Orleans, LA
Abstract Disclosures
Abstract:
Background: High-dose testosterone (HDT) is active in mCRPC pts and may allow successful re-sensitization to previously utilized androgen-axis targeted therapies. The relationship of genomic alterations in AR gene to HDT responsiveness is unclear. Methods: Analysis of consecutive pts treated with ≥1 dose of HDT (testosterone cypionate q 2-4 weeks n = 29; continuous gel n = 4). Baseline characteristics, ctDNA data (Guardant360), and clinical outcomes were assessed. Presence of genomic AR alterations included amplifications (amps) and mutations (muts); all muts had allele fraction ≥0.3%. PSA response rates included PSA declines of > 30% or ≥50%. PSA-progression-free survival (PSA-PFS) was defined as HDT start date to PSA ≥ 25% over baseline after a second confirmed PSA rise. Results: Between May 2016 and Feb 2018, 33 mCRPC pts had median age 73 (58-85), 39% Gleason 8-10, 100% bone mets, 24% nodes + bone, and median baseline PSA level 36.1 ng/mL (0.04-1290). HDT was given post-median of 2 (1-10) CRPC therapies. 73% (24/33) of pts previously received abiraterone (n = 14), enzalutamide (n = 4), or both sequentially (n = 6) prior to HDT for a median of 10.5 months (0.7-56.8). Baseline ctDNA showed 42% AR alterations (amps = 8, muts = 4, both = 2); 33% TP53, and 6% DNA repair (ATM n = 1; BRCA2 n = 1). With median follow-up 4.4 months, HDT given for median of 4.2 months (95% CI, 3.6-4.8); 29% had PSA ≥50% response and 45% PSA ≥30% response. Median PSA-PFS is immature at 5.5 months (95% CI, 1.5-9.5); 14 pts still on HDT treatment. Grade ≥3 AEs were observed in 6% of pts (G4 thrombocytopenia = 1; G4 asthenia = 1). For pts with baseline AR alterations and HDT treatment, repeated ctDNA assays (n = 7) showed that 100% had decreased AR alterations. No relationship between PSA response and baseline ctDNA AR characteristics are discerned at this time. Conclusions: HDT was safe and active in a subset of mCRPC. Responses were clearly noted for men receiving continuous daily testosterone gels, thus continuously high testosterone levels are active in addition to injection-induced bipolar changes. Further understanding of the genomic alterations predicting responsiveness to HDT in mCRPC is required."
