6P Combined analysis of the HER2DX genomic tool in adjuvant APT and ATEMPT trials

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In the APT and ATEMPT trials, adjuvant paclitaxel and trastuzumab (TH) and T-DM1 were found associated with excellent long-term outcomes for patients (pts) with small, node-negative HER2-positive breast cancer (HER2+ BC), respectively. HER2DX risk score was found associated with outcomes in both trials, separately. We conducted a retrospective analysis combining pts included in the APT and ATEMPT trials with available HER2DX data. Co-primary endpoints were associations of HER2DX with relapse-free interval (RFI) and invasive disease-free survival (iDFS). The HER2DX risk-score was evaluated i) as a continuous variable (0-100), ii) using the predefined cut-off (50), and iii) using an exploratory optimal cut-off (32). The Kaplan-Meier method and stratified Cox regression models were used to evaluate the association between HER2DX and outcomes. In total, 471 pts receiving TH (n=324) or T-DM1 (n=147) were included in the study, most having stage I (n=432, 92%) and hormone receptor-positive disease (n=335, 75%). The median follow-up was 6.7 years (10.8 and 5.8 for APT and ATEMPT, respectively). The median HER2DX risk-score was 13.9 (IQR 4.7 - 27.0), with 5.5% and 18.3% of the pts having HER2DX high-risk disease according to the predefined and optimal cut-off, respectively. HER2DX risk score as a continuous variable was associated with RFI (HR per 10-units: 1.39, 95%CI: 1.09-1.78; p=0.009) but not with iDFS (HR per 10-units: 1.18, 0.98-1.42; p=0.09). Using the predefined cut-off (50), pts with HER2DX high-risk disease had higher RFI risk (HR: 7.33, 2.29-23.47, p<0.001), but the effect on iDFS was non-significant (HR: 2.78, 0.97-7.95, p=0.057). In multivariable analysis of RFI, HER2DX remained statistically significant after adjustment for hormone receptor status and tumor size (HR: 7.89, 2.06-30.22, p=0.003). The optimal cut-off (32) distinguished pts with low-risk (7-year RFI of 98.2%; 96.7%-99.6%) from high-risk disease (7-year RFI: 88.7%; 80.4%-97.8%) [delta of 9.5%], including in multivariable analysis for RFI (HR: 6.87, 2.22-21.27, p<0.001) and iDFS (HR: 2.81, 1.26-6.23, p=0.01). The HER2DX risk score is associated with the risk of recurrence among pts with small, node-negative HER2+ breast tumors treated with adjuvant TH or T-DM1.