Gupta Discusses T-DM1’s Role in HER2+ Breast Cancer Treatment

Tanya Gupta, MD, medical oncologist in the Stanford University Department of Medicine, Division of Medical Oncology, discusses the use of ado-trastuzumab emtansine (T-DM1; Kadcyla) for the treatment of patients with HER2-positive breast cancer.

Ado-trastuzumab emtansine, which combines trastuzumab with a cytotoxic agent, was the first antibody-drug conjugate (ADC) to be approved in the HER2-positive space in 2013. This approval was largely supported by findings from the KATHERINE study (NCT01772472). The phase 3 clinical trial sought to compare adjuvant T-DM1 with trastuzumab in patients with HER2-positive early breast cancer who had residual invasive disease after receiving neoadjuvant therapy.

In the study, T-DM1 was shown to significantly improve outcomes for patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant therapy. T-DM1 significantly improved invasive disease-free survival, reducing the risk of recurrence or death by 50% compared with trastuzumab, setting a new standard of care for this patient population.

While T-DM1 remains a mainstay of treatment for patients with HER2-positive disease, Gupta explains that newer ADCs like fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd), and sacituzumab govitecan (Trodelvy) are advancing the field even further. Newer ADCs like these continue to improve outcomes for patients with difficult-to-treat breast cancers.

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0:09 | T-DM1 is indicated for both adjuvant HER2-positive disease and metastatic HER2-positive disease. In the adjuvant setting, it is specifically indicated for patients who have been treated neoadjuvantly and then have residual disease at the time of surgery based on the results of the KATHERINE study [NCT01772472]. This study demonstrated that adjuvant T-DM1 is associated with an improved median overall survival and invasive disease-free survival as compared [with] adjuvant trastuzumab.

0:43 | Now, in the metastatic setting, T-DM1 has been shown to be more efficacious than capecitabine and lapatinib [Tykerb] as based on the EMILIA trial [NCT00829166]. And because of this, for some time, T-DM1 was our favored second-line therapy for metastatic HER2-positive disease. But as we will discuss, T-DXd is now the favored second-line therapy.