Katherine D. Crew, MD, MS, director of Clinical Breast Cancer Prevention Program, Columbia University Irving Medical Center, and director of DataBase Shared Resource at Herbert Irving Comprehensive Cancer Center, Columbia University, discusses treatment for patients with favorable-risk early-stage HER2-positive breast cancer.

The majority of patients with small HER2-positive breast cancer, such as stage I or screen-detected disease, are excluded from large adjuvant trials with trastuzumab (Herceptin), says Crew. However, in the phase II APT trial, women with node-negative disease and tumors ≤3 cm received weekly paclitaxel and trastuzumab for 12 cycles followed by adjuvant trastuzumab. The 7-year update, which was published in the 

 in 2019, demonstrated an excellent disease-free survival (DFS) and overall survival benefit with this approach, says Crew. These data suggest that patients with favorable-risk disease may not need intensive chemotherapy with anthracyclines, adds Crew.

The phase II ATEMPT trial, which was presented at the 2019 San Antonio Breast Cancer Symposium, also evaluated the intensity of treatment in favorable-risk patients. Patients were randomized to receive either trastuzumab emtansine (T-DM1; Kadcyla) for 1 year versus weekly trastuzumab and paclitaxel. The 3-year DFS and recurrence-free survival with T-DM1 was 97.7% and 99.1%, respectively. Notably, trastuzumab and paclitaxel caused more acute neuropathy, but long-term T-DM1 was associated with abnormal liver function tests and thrombocytopenia that led to early discontinuation of treatment, says Crew. Given the toxicity profile of T-DM1, it may not be an optimal choice for patients with favorable-risk disease, concludes Crew.

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Katherine Crew, MD, MS, discusses treatment for patients with favorable-risk early-stage HER2-positive breast cancer.

Dr. Crew on Treatment in Favorable-Risk HER2+ Breast Cancer

Katherine Crew, MD, MS, associate professor, Columbia University Irving Medical Center, discusses new research in the advanced HER2-positive breast cancer landscape.

At the 2019 San Antonio Breast Cancer Symposium, there were 5 trials presented in the HER2-positive breast cancer paradigm. Two of the trials were simultaneously published in the 

The first study, called HER2CLIMB, looked at a new TKI called tucatinib in the third-line metastatic setting with a heavily pretreated population. The other unique aspect of the study was that they included patients with untreated or progressing brain metastases; HER2-positive breast cancer has a propensity for going to the brain and up to 50% of patients with HER2-positive metastatic breast cancer can develop disease in the central nervous system. When tucatinib was added to trastuzumab (Herceptin) and capecitabine (Xeloda) chemotherapy, it led to a significant improvement in progression free survival (PFS) and overall survival. The HER2CLIMB study has changed the standard of care for patients in the third-line metastatic setting of HER2-positive disease, says Crew.

The other intriguing trial was DESTINY-Breast01; patients were treated with an antibody-drug conjugate called fam-trastuzumab deruxtecan-nxki (Enhertu). The open-label, single-group, phase II study showed that fam-trastuzumab deruxtecan-nxki elicited a high overall response rate in a heavily pretreated metastatic HER2-positive population. It more than doubled the PFS that is expected in such a population, concludes Crew.

Katherine Crew, MD, MS, discusses new research in the advanced HER2-positive breast cancer landscape.
 
 

Katherine Crew, MD, MS

Articles

Dr. Crew on Treatment in Favorable-Risk HER2+ Breast Cancer

Dr. Crew on New Research in Advanced HER2+ Breast Cancer