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Options Shift Paradigm of Locally Advanced HER2+ Breast Cancer

Gina Columbus @ginacolumbusonc
Published: Monday, Feb 18, 2019

Theresa Shao, MD

Theresa Shao, MD

In locally advanced HER2-positive breast cancer, the additions of agents such as neratinib (Nerlynx) and pertuzumab (Perjeta) in the adjuvant setting, as well as pertuzumab in the neoadjuvant setting, have led to an improvement in invasive disease- free survival (iDFS) for patients, explained Theresa Shao, MD.

State of the Science Summit™ on Breast Cancer, Shao, an assistant professor of hematology-oncology at Mount Sinai Hospital, discussed the neoadjuvant and adjuvant findings with pertuzumab as well as the adjuvant use of neratinib in patients with locally advanced HER2-positive breast cancer.

OncLive®: Could you discuss the use of pertuzumab in the locally advanced setting of breast cancer?

Shao: With pertuzumab, the data we have in the neoadjuvant setting are in 2 studies, NEOSPHERE and TRYPHAENA, that I talked about [at this meeting]. We showed that the addition of pertuzumab as neoadjuvant therapy with chemotherapy and trastuzumab improved pathological complete response. In the adjuvant setting, we have the APHINITY data, in which the addition of pertuzumab to chemotherapy plus trastuzumab improved iDFS at 3 years.

What data exist with neratinib in the adjuvant space?

This is a small molecule, irreversible tyrosine kinase inhibitor of HER1/HER3/HER4. The study that I spoke about is the ExteNET trial, which looked at neratinib in the extended adjuvant therapy setting. Patients had prior treatment with trastuzumab, and they started this drug after 1 year of completing trastuzumab. This study showed that the addition of neratinib for another year has improved iDFS as well, and it was mostly seen in patients with ER-positive and node-positive disease. Therefore, patients with higher-risk disease, and also ER-positive disease, have benefit.

There have been toxicity concerns with neratinib. How have we incorporated this agent into practice?

The main concern from the study was that 40% of patients on study had grade 3 diarrhea; quite a high number of patients discontinued the therapy early on, so there was a lot of concern from the physicians and patients who [were unsure how to apply] this is if there is so much diarrhea.
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