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Association details:
| Biomarker: | AR amplification |
|---|---|
| Cancer: | Prostate Cancer |
| Drug: | Xtandi (enzalutamide capsule) (Androgen receptor inhibitor) |
| Direction: | Resistant |
Evidence:
Source:
Title:
Real-world overall survival (OS) and time to therapy discontinuation (TTD) of patients (pts) with mCRPC treated with second-generation novel hormonal therapies (NHT) associated with tissue-based comprehensive genomic profiling (CGP)
Published date:
02/08/2021
Excerpt:
We sought to correlate real-world outcomes on NHT with comprehensive genomic profiling (CGP)-reported alterations, hypothesizing that AR amplification (ARamp) and deleterious genomic alterations (GAs) in BRCA2, PTEN, RB1, TP53 would correlate with worse outcomes on NHT. Abiraterone (n = 242; 61%) and enzalutamide (n = 145; 39%) were most common NHTs. As hypothesized, ARamp correlated with worse TTD (aHR: 3.37 [1.26-9.0]) and OS (aHR: 4.92 [1.47-16.5]). BRCA2 GA correlated with improved OS (aHR: 0.41 [0.21-0.81]), but no differences in TTD (aHR: 1.25 [0.82-1.9]). RB1 GA had trends for worse OS (aHR: 2.0 [0.93-4.28]) and worse TTD (aHR – 1.41 [0.72-2.8]). TP53 GA had worse OS (aHR: 1.47 [1.1-2.0]), but no difference in TTD (aHR: 1.08 [0.85-1.4]),...ARamp is associated with worse TTD and OS in mCRPC pts treated with NHT in real-world. Surprisingly, BRCA2 GA correlated with improved OS but not TTD.
DOI:
10.1200/JCO.2021.39.6_suppl.142
Source:
Title:
PROSENZA: Prospective Multi-Centre Study of Prognostic Factors in mCRPC Patients Treated With Enzalutamide.
Excerpt:
...To assess the prognostic value for overall survival of androgen receptor splicing variant 7 (AR-V7) and/or AR amplification in mCRPC patients...
Trial ID:
Title:
Androgen receptor gain in circulating free DNA and splicing variant 7 in exosomes predict clinical outcome in CRPC patients treated with abiraterone and enzalutamide
Published date:
01/26/2021
Excerpt:
Eighty-four mCRPC patients received abiraterone (n = 40) or enzalutamide (n = 44) as first-line therapy. Twelve patients (14.3%) presented AR gain and 30 (35.7%) AR-V7+ at baseline. Median progression-free survival (PFS) and overall survival (OS) were significantly longer in AR-V7- vs AR-V7+ patients (24.3 vs 5.4 months, p < 0.0001; not reached vs 16.2 months, p = 0.0001, respectively)...The AR gain/AR-V7 combined analysis confirmed a strong predictive effect for biomarkers combination vs patients without any AR aberration (PFS 3.8 vs 28 month, respectively; OS 6.1 vs not reached, respectively; p < 0.0001).
DOI:
10.1038/s41391-020-00309-w
Source:
Title:
AR enhancer and locus genomic alterations as cell-free DNA biomarkers of primary resistance to AR-directed treatment of metastatic prostate cancer.
Published date:
05/13/2020
Excerpt:
AR/enhancer alterations (copy gain, tandem duplication, and point mutation) in cfDNA were strongly predictive of primary resistance to AR-directed therapy (PPV = 100%, Sens. = 89%).
DOI:
10.1200/JCO.2020.38.15_suppl.5529
Source:
Title:
Plasma cell-free DNA (cfDNA) profiling of copy number variation (CNV) to identify poor prognostic biomarkers in metastatic castration-resistant prostate cancer (mCRPC).
Published date:
02/13/2020
Excerpt:
OS was significantly decreased in patients with PI3KCA gain (median 21.7 mo vs 6.6 mo, p < 0.0001), PTEN loss (24.8 mo vs 11.7 mo, p = 0.0019) and AR gain (21.7 mo vs 12.0 mo, p = 0.0083). Furthermore, all three alterations independently predicted for poor survival in multivariable analyses (MVA; Table). Findings in the independent cohort showed similar OS results in MVA: PIK3CA gain (HR 2.0, p = 0.07), PTEN loss (HR 1.7, p = 0.08) and AR gain (HR 1.7, p = 0.03).
