Katherine D. Crew, MD, MS, the director of Clinical Breast Cancer Prevention Program at Columbia University Irving Medical Center and director of DataBase Shared Resource at Herbert Irving Comprehensive Cancer Center of Columbia University, discusses recent advances made in HER2-positive breast cancer treatment.

The space has seen a huge explosion of HER2 targeted therapies in recent years, says Crew. The field now has 3 different classes of drugs that are under investigation at the moment: CDK4/6 inhibitors, mTOR inhibitors, and PI3K inhibitors. As a result of these efforts, the survival of patients with HER2-positive disease—which has traditionally been considered to be a more aggressive form of breast cancer&mdash;has significantly improved, says Crew. The median survival of patients with metastatic disease is now approaching 5 years.

Additionally, many of these newer drugs are also being examined in the adjuvant setting for early-stage disease in patients who are being treated for curative intent, adds Crew. Another interesting area of research is focused on exploring the idea of deescalating therapy. Adding more drugs to the mix can also add cost and toxicity; as such, it’s important to also look into the potential to de-escalate therapies in favorable patients, so they can be spared from some of the long-term toxicities, concludes Crew.

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Katherine D. Crew, MD, MS, discusses recent advances made in HER2-positive breast cancer treatment.

Dr. Crew on Recent Advances in HER2+ Breast Cancer

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 updated data with margetuximab in HER2-positive breast cancer.

The phase III SOPHIA trial evaluated the monoclonal antibody margetuximab versus trastuzumab (Herceptin) in combination with investigator's choice of chemotherapy as third-line therapy in patients with metastatic HER2-positive disease. Patients had to have received 1 to 3 prior lines of therapy in the metastatic setting to be eligible for enrollment. The initial results showed modest improvements in objective response and progression-free survival, says Crew.

Data from the second interim analysis presented at the 2019 San Antonio Breast Cancer Symposium did not show a significant difference in overall survival (OS) with margetuximab. However, an exploratory analysis showed that a subset of patients with the CD16A-F allele experienced a trend toward improved OS.

Dr. Crew on Updated Data With Margetuximab in HER2+ Breast Cancer

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 the results of the APHINITY trial in HER2-positive breast cancer.

The APHINITY trial examined pertuzumab (Perjeta) added to trastuzumab (Herceptin) and standard chemotherapy in patients with operable HER2-positive breast cancer who were either node-positive or high-risk node-negative, explains Crew. The addition of trastuzumab in the adjuvant setting improves invasive disease-free survival (iDFS) for patients with HER2-positive disease, and the APHINITY trial demonstrated a modest iDFS improvement with dual-HER2 blockade, says Crew.

The second interim analysis of the APHINITY trial, which was presented during the 2019 San Antonio Breast Cancer Symposium, showed continued improvement in iDFS with the adjuvant combination of trastuzumab and pertuzumab (Perjeta); however, most of the benefit occurred in patients with node-positive disease. Therefore, the addition of pertuzumab to trastuzumab is standard for patients with node-positive, HER2-positive breast cancer, according to Crew.

Many patients who have stage II disease should be receiving trastuzumab or pertuzumab in the neoadjuvant setting, says Crew. There are certain advantages to downstaging and assessing tumor sensitivity based on whether the patient develops a pathologic complete response, concludes Crew.

Katherine D. Crew, MD, MS, discusses the results of the APHINITY trial in HER2-positive breast cancer.

Katherine D. Crew, MD, MS

Articles

Dr. Crew on Recent Advances in HER2+ Breast Cancer

Dr. Crew on Updated Data With Margetuximab in HER2+ Breast Cancer

Dr. Crew on the APHINITY Trial Results in HER2+ Breast Cancer