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Trastuzumab Deruxtecan Efficacious in Breast Cancer Across Varying HER2 Levels

Angelica Welch
Published: Wednesday, Jun 13, 2018

Hiroji Iwata, MD, PhD

Hiroji Iwata, MD, PhD

Long-term findings from a phase I study of trastuzumab deruxtecan (DS-8201a) showed that the investigational HER2-targeting antibody-drug conjugate had antitumor activity in multiple tumor types that expressed HER2 at varying levels. Lead author Hiroji Iwata, MD, PhD, said that the activity observed with DS-8201a may shift the definition of HER2expression in cancer.

, Iwata, vice director and chief of Breast Oncology at Aichi Cancer Center Hospital, discussed the promise of DS-8201a in breast cancer or other solid tumors with HER2 expression.

OncLive: Can you provide some background on DS-8201a?

Iwata: The HER2-positive population is sensitive to anti-HER2 therapies, and the activity is very promising in metastatic breast cancer. However, the HER2/low breast cancer population does not show as promising of results when using these anti-HER2 therapies. DS-8201a is a very promising drug, and a competitor to anti-HER2 antibody with a similar molecular payload. The characteristic of DS-8201a that is very promising is the bystander effect. Bystander effect permeates on the membrane, so the result is not only beneficial for HER2-overexpressing patients, but patients who are HER2/low. 

The bystander effect is a very promising characteristic. Therefore, it is promising in HER2/neu or HER2-low breast cancer and gastric cancer.

What are the significance of the findings?

These phase I data are not only important for breast and gastric cancer, but also for any other cancer with HER2 overexpression or with a HER2-mutant cohort. Those patients can achieve good results using DS-8201a. The breast and gastric cancer population is a very heavily pretreated one and there is a high response here, which is important. 

Data with DS-8201a are promising. Both the FDA and the Japan's Pharmaceuticals and Medical Devices Agency consider it a breakthrough therapy. 

What would be the optimal sequencing for this agent?

The next step after standard frontline therapy would be where we use DS-8201a. In the future, it may enter the frontline [setting] as a standard of care as new data are obtained. I hope DS-8201a will become a new standard for HER2-positive metastatic breast cancer and for the HER2/low population.  

Are there any next steps?

Based on the DS-8201a study, the definition of HER2 expression should be changed. Right now, the definition of HER2 expression is overexpression, but DS-8201a has good activity in HER2/low patients, as well. Perhaps in the future, the definition of HER2 should be changed to include low, medium, and high [expressors]. The definition is very important. 
Iwata H, Tamura K, Doi T, et al. Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts. J Clin Oncol. 2018;36(suppl; abstr 2501).

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