Kelly E. Westbrook, MD, assistant professor, Duke University School of Medicine, discusses combatting tumor heterogeneity in patients with HER2-positive breast cancer.

Ado-trastuzumab emtansine (T-DM1; Kadcyla) is one antibody-drug conjugate currently in clinical trials with a high affinity for the HER2 receptor that treats HER2-positive cells with minimal toxicity because of low levels of T-DM1 systemically, explains Westbrook. However, it does not have the ability to target patients with low expression of HER2 cells, says Westbrook.

There are many interesting transitions in the antibody-drug conjugate world, including trying to create antibody-drug conjugates that will have an affinity for low levels of HER2 cells or a bystander effect, according to Westbrook. Traditional therapy is not affected by tumor heterogeneity because most HER2-targeted therapies are coupled with a chemotherapy backbone, which helps navigate the tumor heterogeneity, concludes Westbrook.

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Kelly E. Westbrook, MD, discusses combatting tumor heterogeneity in patients with HER2-positive breast cancer.

Dr. Westbrook on Combatting Tumor Heterogeneity in HER2+ Breast Cancer

Kelly E. Westbrook, MD, assistant professor, Duke University School of Medicine, discusses the 3-year follow-up data on the KRISTINE trial in stage II or III HER2-positive breast cancer.

The disease-free survival from the time of surgery for trastuzumab (Herceptin), pertuzumab (Perjeta), docetaxel, and carboplatin (TCHP) versus ado-trastuzumab emtansine (T-DM1; Kadcyla) plus pertuzumab was not significantly different, explains Westbrook. However, event-free survival at 3 years was higher for the TCHP arm at 94.2% versus 85.3% in the T-DM1 plus pertuzumab arm. The Kaplan-Meier curve shows the failure of the T-DM1 plus pertuzumab regimen in the neoadjuvant setting, says Westbrook.

Researchers hypothesize the reason for the T-DM1 plus pertuzumab failure is related to tumor heterogeneity, according to Westbrook. Patients who get T-DM1 plus pertuzumab are only getting therapy that is targeted at the HER2 receptor if there are cells not significantly HER2 overexpressing. There is no chemotherapy backbone in that regimen to offer for treatment of that portion of the tumor, Westbrook concludes.

Kelly E. Westbrook, MD, discusses the 3-year follow-up data on the KRISTINE trial in stage II or III HER2-positive breast cancer.

Kelly E. Westbrook, MD

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Dr. Westbrook on Combatting Tumor Heterogeneity in HER2+ Breast Cancer

Dr. Westbrook on 3-Year Follow-Up Data of the KRISTINE Trial in HER2+ Breast Cancer