Sequential Therapy With HER2 Tyrosine Kinase Inhibitors in Patients With HER2-Positive Metastatic Breast Cancer

HER2-targeted tyrosine kinase inhibitors (TKIs) tucatinib, lapatinib and neratinib are standard agents for treatments of HER2-positive (HER2+) metastatic breast cancer. Due to their penetration through the blood-brain barrier, these agents are especially beneficial for patients with brain metastases. To date, limited data exists on the sequential use of different HER2-targeted TKIs, and it is unknown if reusing the same TKI as a part of different treatment regimens provides clinical benefits.

We performed a retrospective single institution study (IRB 23-2337) and identified N = 105 patients with HER2+ metastatic breast cancer and a TKI regimen of at least 1 month. We then performed a manual abstraction to identify patients who had at least 2 TKI regimens (N = 24) and estimated time on treatment (median and range in months). Best responses to TKI treatments were evaluated by MD review. Patients were censored at the time of the last follow up when the end of treatment data were not available.

In our patient cohort, 14 of 24 patients (58%) stayed on the second or third TKI regimen for greater than 6 months, and 10 of 24 patients (42%) were on the subsequent TKI regimen(s) for longer than the first one. Time on a non-TKI regimen between the first and second TKI was not associated with the duration of benefit from the second TKI.

Our data support using different HER2-targeted TKI regimens in sequence, offering additional effective treatment options for patients with HER2+ metastatic breast cancer, including patients with brain metastases.