Neratinib, fulvestrant, trastuzumab combo aids metastatic breast cancer

For patients with hormone receptor (HR)-positive HER2-mutant metastatic breast cancer (MBC) with progression on cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy, neratinib + fulvestrant + trastuzumab (N + F + T) is beneficial, according to a study published in the October issue of the Annals of Oncology.

Komal Jhaveri, M.D., from the Memorial Sloan Kettering Cancer Center in New York City, and colleagues reported results from 71 patients with HR-positive HER2-negative MBC with activating HER2 mutations and prior CDK4/6i therapy. Patients received N + F + T or F + T or fulvestrant alone. Those with disease progression on F + T or fulvestrant alone could cross over to N + F + T.

The researchers found that the objective response rate was 39 percent for 57 N + F + T-treated patients, and median progression-free survival was 8.3 months. There were no responses in the F + T or fulvestrant-treated patients, but responses were seen in those crossing over to N + F + T.

Patients with ductal and lobular histology, one or more than one HER2 mutations, and co-occurring HER3 mutations had responses. Acquisition of additional HER2 alterations and mutations in genes including PIK3CA were revealed on longitudinal circulating tumor DNA sequencing, enabling further precision targeting and possible re-response.

"This novel combination therapy showed very encouraging results, even in patients who failed several other lines of treatment," co-author Carlos L. Arteaga, M.D., from UT Southwestern Simmons Comprehensive Cancer Center in Dallas, said in a statement.

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