Currently Accepted Regimens: NCCN Guidelines

Sara A. Hurvitz, MD: The latest version of the NCCN (National Comprehensive Cancer Network) guidelines in 2020 lists a number of treatment options for patients who are being treated in the third-line setting for HER2-positive metastatic breast cancer. There have been 3 new additions, including neratinib plus capecitabine; tucatinib plus capecitabine; and trastuzumab,or T-DXd, trastuzumab deruxtecan. All 3 of these agents have been FDA approved in the last 7 months or so and are available to our patients.

In addition to these exciting regimens that are newer to the approval list, we also have a number of other treatment options available for patients who have progressed after frontline THP (docetaxel, trastuzumab, and pertuzumab) and second-line T-DM1 (trastuzumab emtansine). These include the use of trastuzumab combined with single-agent chemotherapy, and a number of options are available. One of my favorites is vinorelbine because it’s so well tolerated, but other drugs, including gemcitabine, eribulin, and taxane, also are good, appropriate options.

You can also combine trastuzumab with lapatinib. Kim Blackwell’s (MD) phase 3 trial showed that this combination was associated with better survival compared with lapatinib alone in patients who’d progressed on trastuzumab.

Then, for patients whose tumors co-express the hormone receptors, you can combine trastuzumab or lapatinib with endocrine therapy—an aromatase inhibitor, a SERD (selective estrogen receptor degrader), a SERM (selective estrogen receptor modulator).

There are emerging data regarding the use of CDK4/6 (cyclin-dependent kinases 4 and 6) inhibitors in hormone-receptor positive, HER2-positive breast cancer from the monarcHER study. However, this is not yet FDA approved, so we’ll have to look for further data relating to that.

Transcript edited for clarity.