Investigational Targeted Therapies for Breast Cancer

One approach to targeted therapies for breast cancer has been the development of the antibody-drug conjugate (ADC), says Ian E. Krop, MD.This approach combines a monoclonal antibody specific for a cell-surface protein with a cytotoxic agent, which is delivered directly to the cancer cell. Trastuzumab emtansine, or T-DM1, is a HER2-specific ADC that has demonstrated activity in metastatic HER2-positive breast cancers.

CDX-011 is an investigational ADC that targets GPNMB, a cell-surface protein that is predominantly expressed in triple-negative breast cancer (TNBC). Smaller studies evaluating CDX-011 have shown significant response rates, particularly in TNBC. An ongoing randomized trial is assessing single-agent CDX-011 compared with capecitabine in the TNBC. Another ADC, IMMU-132, targets TROP-2, and has shown activity in pretreated TNBC, adds Krop.

Several breast cancers may have amplification of the FGFR pathway, which is an essential mechanism of disease resistance to HER2-targeted treatments, endocrine therapy, and chemotherapy, explains Ingrid A. Mayer, MD. The presence of FGFR amplification may suggest early disease recurrences and unfavorable responses with conventional therapies.

Lucitanib is a potent FGFR inhibitor under investigation in individuals with metastatic breast cancer. Patients who have an FGFR1 amplification and an alteration such as FGF3, FGF4, or FGR19 are the most likely to benefit. One of the challenges is managing the side effects when adding these drugs to conventional treatments, such as endocrine therapies, that are well tolerated, comments Mayer.