William Gradishar, MD, chief of hematology and oncology, Department of Medicine, Betsy Bramsen Professorship of Breast Oncology, and professor of medicine, hematology and oncology, Northwestern University Feinberg School of Medicine, discusses factors to consider when determining the optimal treatment of patients with HER2-positive breast cancer.

When a new therapy is introduced into the treatment armamentarium for this patient population, it is important to examine whether the agent will be effective in earlier phases of disease, according to Gradishar. Ongoing studies are examining ado-trastuzumab emtansine (T-DM1; Kadcyla) vs fam-trastuzumab deruxtecan-nxki (Enhertu), and tucatinib (Tukysa) is being examined in combination with T-DM1, Gradishar says. Results from these studies could impact how these drugs are utilized in the treatment of patients, Gradishar notes. 

In terms of integrating novel therapies into the treatment algorithm, it is important to consider any prior therapies the patient has received and how recently, Gradishar adds. For example, if patient who has residual disease postoperatively is given T-DM1, that will factor into whether they receive the agent again upon the development of metastatic disease or whether they should receive a newer treatment option, Gradishar explains. Additionally, whether a patient develops brain metastases is an important factor to consider when deciding treatment. If these metastases are present, tucatinib would be a beneficial option, Gradishar concludes.

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William Gradishar, MD, discusses factors to consider when determining the optimal treatment of patients with HER2-positive breast cancer.


Dr. Gradishar on Integrating Novel Options Into the HER2+ Breast Cancer Treatment Algorithm

William J. Gradishar, MD, chief of hematology and oncology, Department of Medicine; Betsy Bramsen Professorship of Breast Oncology; and a professor of medicine (hematology and oncology) at Northwestern University Feinberg School of Medicine, discusses the expanding role of fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive breast cancer.

Trastuzumab deruxtecan is an antibody-drug conjugate (ADC) that has a similar mechanism ​of action as ado-trastuzumab emtansine (T-DM1; Kadcyla), Gradishar explains. ​Trastuzumab deruxtecan contains the monoclonal antibody trastuzumab ​(Herceptin), which binds to HER2, a ​stable linker and a cytotoxic payload.

However, trastuzumab deruxtecan has a greater number of payloads per antibody compared with T-DM1, ​says Gradishar.

Notably, trastuzumab deruxtecan has been a ​welcome addition to the HER2-positive breast cancer armamentarium, ​Gradishar says. The agent is current being evaluated in a head-to-head trial with T-DM1 to determine how the agents compare in terms of efficacy and safety.

In several studies, trastuzumab deruxtecan demonstrated meaningful clinical activity in patients, including those who received prior T​-DM1. Now, the agent is approved for use in the metastatic setting, Gradishar concludes.

William J. Gradishar, MD, discusses the expanding role of fam-trastuzumab deruxtecan-nxki in HER2-positive breast cancer.

Dr. Gradishar on the Expanding Role of Trastuzumab Deruxtecan in HER2+ Breast Cancer

William Gradishar, MD, Betsy Bramsen Professorship of Breast Oncology, Professor in Medicine-Hematology/Oncology, Northwestern University Feinberg School of Medicine, discusses changes to the NCCN Breast Cancer Guidelines.

One of the most significant changes in the guidelines is that duel-targeting of the HER2-pathway for patients with operable HER2-positive breast cancer is now recommended, says Gradishar. This change was based on the NeoSphere trial, which showed that the use of pertuzumab and trastuzumab with chemotherapy improved pathological complete response versus other regimens. This may lead to improved outcomes overall, says Gradishar.

In hormone receptor-positive metastatic disease, the guidelines now recommend endocrine therapy combined with targeted agents instead of just endocrine therapy alone, says Gradishar. In trials, this combination has translated into a marked improvement in progression-free survival.

William Gradishar, MD,

Articles

Dr. Gradishar on Integrating Novel Options Into the HER2+ Breast Cancer Treatment Algorithm

Dr. Gradishar on the Expanding Role of Trastuzumab Deruxtecan in HER2+ Breast Cancer

Dr. William Gradishar on Updates in NCCN Breast Cancer Guidelines