KEY TAKEAWAYS
- The APT and ATEMPT phase 2 study analyzed the efficacy of adjuvant therapy with TH or T-DM1 in patients with small, node-negative HER2-positive breast cancer.
- The trials’ co-primary endpoints were associations of HER2DX with relapse-free interval and invasive disease-free survival.
- The study established a direct link between the HER2DX risk score and the likelihood of recurrence in patients with small, node-negative HER2+ breast tumors who underwent adjuvant TH or T-DM1 treatment.
The APT and ATEMPT studies demonstrated that adjuvant therapy with paclitaxel and trastuzumab (TH) or T-DM1 was highly efficacious in treating patients (pts) with small, node-negative HER2-positive breast cancer (HER2+ BC), leading to exceptional long-term outcomes. HER2DX risk score was correlated with outcomes in both trials.
Researchers analyzed pts included in the APT and ATEMPT trials with available HER2DX data. The study’s co-primary endpoints included finding the correlation of HER2DX with relapse-free interval (RFI) and invasive disease-free survival (iDFS). The HER2DX risk score was assessed as a continuous variable ranging from 0-100. Researchers utilized a predefined cut-off of 50 and an exploratory optimal cut-off of 32. The Kaplan-Meier method and stratified Cox regression models were employed to determine the association between HER2DX and outcomes.
In the trial, 471 pts were administered TH (n=324) or T-DM1 (n=147). Most patients had stage I (92%) and a hormone receptor-positive disease (75%). The median follow-up was also 6.7 years (10.8 and 5.8 for APT and ATEMPT, respectively). The median HER2DX risk-score stood at 13.9 (IQR 4.7 – 27.0). It’s worth noting that 5.5% and 18.3% of the pts were diagnosed with HER2DX high-risk disease according to the predefined and optimal cut-off, respectively. HER2DX risk score, when regarded as a continuous variable, had a significant correlation with RFI (HR per 10-units: 1.39, 95%CI: 1.09-1.78; p=0.009). However, it had no association with iDFS (HR per 10-units: 1.18, 0.98-1.42; p=0.09). The pts with high-risk HER2DX disease have a higher risk of recurrence-free interval (RFI)(HR: 7.33, 2.29-23.47, p<0.001) than those with low-risk disease. The effect on invasive disease-free survival (iDFS) may not be influential (HR: 2.78, 0.97-7.95, p=0.057) when using the cut-off of 50, but HER2DX remains statistically substantial in RFI (in multivariable analysis) even after adjusting for hormone receptor status and tumor size (HR: 7.89, 2.06-30.22, p=0.003). Using an optimal cut-off of 32 pts with low-risk disease (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 critical in determining the probability of cancer recurrence in pts with small, node-negative HER2+ breast tumors who underwent adjuvant TH or T-DM1 treatment.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT01853748
Tarantino, P., Villacampa, G., Graham, N., Waks, A.G., Gonzalez, P.V., Brasó-Maristany, F., Torres, E. S., Galván, P., Brunet, L. P., Demeo, M.K., Partridge, A.H., Burstein, H.J., Krop, I., Tayob, N., Winer, E.P., Prat, A., Tolaney, S.M. Annals of Oncology (2023) 8 (1suppl_4): 101218-101218. 10.1016/esmoop/esmoop101218.
