William R. Gwin III, MD

William R. Gwin III, MD, acting instructor at the Seattle Cancer Care Alliance and acting instructor of the Tumor Vaccine Group at the University of Washington School of Medicine, discusses potential areas of investigation with the combination of alpha-tocopheryloxyacetic acid (alpha-TEA) and trastuzumab (Herceptin) in breast cancer.

During the 2020 ASCO Virtual Scientific Program, preliminary safety data from an ongoing phase 1 dose-escalation trial evaluating alpha-TEA/trastuzumab in patients with recurrent HER2-positive metastatic breast cancer were presented. The combination will need to show both clinical efficacy and safety before it is evaluated in a phase 2 trial, explains Gwin.

Looking to the future, it is not unreasonable to believe that the combination could be of benefit in the early-stage HER2-positive setting as well, augmenting pathologic complete response rates in the neoadjuvant setting and decreasing the risk of recurrence in the adjuvant setting. Ongoing research efforts are also testing the agent in combination with checkpoint inhibitors, as a way to provide synergistic benefit to patients with triple-negative breast cancer, concludes Gwin.

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 William R. Gwin III, MD, discusses potential areas of investigation with the combination of alpha-tocopheryloxyacetic acid (alpha-TEA) and trastuzumab (Herceptin) in breast cancer.

Dr. Gwin on Potential Areas of Investigation With Alpha-TEA/Trastuzumab in Breast Cancer

William R. Gwin III, MD, acting instructor at the Seattle Cancer Care Alliance and acting instructor of the Tumor Vaccine Group at the University of Washington School of Medicine, discusses the mechanism of action of alpha-tocopheryloxyacetic acid (α-TEA) in HER2-positive metastatic breast cancer.

It is understood that type 1 (Th1) cells are needed in order to generate antitumor immunity, says Gwin. Unfortunately, Th1 cells are lost in many tumors, adds Gwin. α-TEA appears to augment Th1 immunity by increasing CD4+ Th1 and CD8+ tumor-infiltrating lymphocyte levels and by boosting cytokines associated with Th1, such as interferon gamma.

α-TEA has been reported to augment TH1 immunity through an increase of activated effector memory CD4+ and CD8+ T cells and a decrease of immune suppressive CD4+CD25+ regulatory T cells in the tumor, says Gwin. These results suggest that the agent does mediate antitumor effects, but through the use of different mechanisms: through the generation of reactive oxygen species leading to apoptosis and through an immune-mediated component that drives the augmentation of the effectiveness of CD4+ and CD8+ cells, concludes Gwin.

William R. Gwin III, MD, discusses the mechanism of action of alpha-tocopheryloxyacetic acid in HER2-positive metastatic breast cancer.

Dr. Gwin on the Mechanism of Action of Alpha-TEA in HER2-Positive Metastatic Breast Cancer

William R. Gwin III, MD, acting instructor, Seattle Cancer Care Alliance, acting instructor, Tumor Vaccine Group, University of Washington School of Medicine, discusses the safety profile of alpha-tocopheryloxyacetic acid (α-TEA) in combination with trastuzumab (Herceptin) in recurrent HER2-positive metastatic breast cancer.

As part of the 2020 ASCO Virtual Scientific Program, preliminary safety data from an ongoing phase 1 dose-escalation trial evaluating α-TEA/trastuzumab in this patient population were presented.

As of May 2020, patients enrolled in the study were receiving the third dose level of the combination, says Gwin.

Regarding safety, the regimen appeared to be well tolerated, with the most common adverse effects being grade 1/2, says Gwin.

Notably, an increased incidence of atrial fibrillation was observed with the combination, says Gwin. However, further analysis indicated that the patients who developed this toxicity had been predisposed to atrial fibrillation in the past.

As such, patients with atrial fibrillation will be excluded from the trial going forward, concludes Gwin.

William R. Gwin III, MD, discusses the safety profile of alpha-tocopheryloxyacetic acid in combination with trastuzumab in recurrent HER2-positive metastatic breast cancer.

Author | William R. Gwin III, MD

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