Nusayba Bagegni, MD, discusses updated efficacy and biomarker data from the phase 2 APT and ATEMPT trials in early-stage HER2-positive breast cancer.
Nusayba Bagegni, MD, assistant professor of medicine, Division of Medical Oncology, Washington University School of Medicine, medical oncologist, Siteman Cancer Center, discusses updated efficacy and biomarker data from the phase 2 APT (NCT00542451) and ATEMPT (NCT01853748) trials in early-stage HER2-positive breast cancer.
The APT trial investigated the administration of adjuvant paclitaxel over the course of 3 months,followed by treatment with trastuzumab (Herceptin) for 9 months in patients with small, node-negative, HER2-positive breast cancer. According to the final 10-year analysis, the regimen produced an invasive disease-free survival (iDFS) rate of 91.3% and a recurrence-free interval (RFI) of 96.3%. Overall, the trial confirmed the regimen's ability to provide long-term survival benefit.
The ATEMPT trial compared the toxicity of ado-trastuzumab emtansine (Kadcyla; T-DM1) with adjuvant paclitaxel plus trastuzumab in patients with stage 1 HER2-positive breast cancer. In this trial, T-DM1 failed to demonstrate superior safety over the combination regimen. Alongside results from APT, these findings have solidified this regimen as the standard of care in stage I HER2-positive breast cancer.
Correlative analyses using the prognostic and predictive HER2DX assay were performed in both the APT and ATEMPT trials, Bagegni states. In the APT trial, HER2DX as a continuous variable was associated with a higher risk of disease recurrence. A HER2DX risk-score of 32 was identified as the optimal cutoff for low vs high risk status. Similarly, patients with HER2DX low-risk disease had a more favorable 5-year RFI and numerically improved 5-year DFS vs those with HER2DX high-risk disease. These data could be used to better predict patient benefit, Bagegni says. For example, patients who initially score worse may be eligible for more aggressive therapy in the future, while those who meet certain cutoffs for the HER2DX scoring system may have a better prognosis, Bagegni explains.
Moreover, PAM50 gene expression analysis indicated that patients with luminal B HER2-positive breast cancer are associated with worse disease-specific outcomes, Bagegni adds. Accordingly, future research efforts should focus on modifying approaches to treatment for this specific subgroup, Bagegni concludes.
Disclosures: Dr. Bagegni reports receiving institutional research funding from Sermonix Pharmaceuticals, Inc, Xcovery Holding Company, LLC, Seattle Genetics, Inc, Ambrx, Inc, Novartis Pharmaceuticals Incorporation, Atossa Therapeutics, Inc, Daiichi Sankyo, AstraZeneca Pharmaceuticals LP, Pfizer Inc, Sarah Cannon Development Innovations, LLC