Table 3.

Individual genomic alterations and their association with TTP

Univariate Cox modelMultivariate Cox model
SubgroupPatients in subgroupMedian TTP (months)% Patients with TTP < 12 weeksHR (95% CI)P valueHR (95% CI)P value
BRCA2/ATM truncating mutation141.869.2%6.14 (3.35–11.26)<0.0015.27 (2.79–9.95)<0.001
BRCA2/ATM monoallelic deletion only222.945.5%2.58 (1.58–4.21)<0.0011.44 (0.82–2.53)0.205
TP53 defect663.348.4%2.70 (1.86–3.91)<0.0011.96 (1.23–3.11)0.005
TP53 defect (two or more)192.762.5%5.65 (3.14–10.17)<0.0013.40 (1.70–6.80)<0.001
RB1 defect373.641.7%2.03 (1.36–3.04)<0.0011.39 (0.96–2.01)0.081
AR gain675.137.5%2.05 (1.43–2.93)<0.0011.21 (0.77–1.91)0.401
AR gain (CN ≥ 8)312.751.7%2.65 (1.68–4.19)<0.0011.48 (0.85–2.58)0.164
AR gain (CN < 8)366.325.7%1.67 (1.07–2.62)0.0251.08 (0.63–1.85)0.772
AR LBD mutation146.27.1%1.02 (0.53–1.95)0.950.82 (0.40–1.68)0.581
PI3K pathway defect593.743.6%2.45 (1.71–3.51)<0.0011.46 (0.94–2.27)0.095
WNT pathway defect164.833.3%1.29 (0.71–2.34)0.3980.67 (0.35–1.28)0.225
SPOP mutation127.38.3%1.00 (0.51–1.97)1.000.43 (0.21–0.89)0.022
ctDNA > 2%1155.431.8%
All patients2027.523.7%
  • NOTE: In each comparison, the analyses compare alteration-positive patients to those where no alteration in the gene/pathway was detected. Each genomic alteration is assessed individually in a multivariate model adjusting for significant clinical prognostic factors and the detection of ctDNA > 2% (Supplementary Table S6). A patient was considered alteration-positive for copy-number changes (e.g., AR gain), somatic rearrangements, and germline homologous recombination repair defects even if the patient had no detectable somatic mutations to quantify ctDNA fraction.