207P Sequential therapy with HER2 tyrosine kinase inhibitors in patients with HER2-positive metastatic breast cancer

Up to 50% of patients (pts) with HER2+ breast cancer will develop brain metastases throughout the course of disease, and approximately 50% of them will die from intracranial disease progression. Tyrosine kinase inhibitors (TKIs) play a significant role in the treatment of HER2+ metastatic breast cancer (MBC) due to their ability to cross the blood brain barrier and prevent and treat brain metastases. In the US, available TKIs include neratinib, lapatinib, and tucatinib, which was approved in 2020 based on the HER2CLIMB trial. There is limited data on the sequential use of these agents. Here we present real-life data on sequential use of TKIs for treatment of HER2+ MBC. We performed a retrospective study (IRB 23-2337) and identified N=109 pts with HER2+ MBC and a TKI regimen with duration of ≥1 month. We then performed a manual abstraction to identify pts who had at least 2 TKI regimens and calculated time on treatment (median and range in months). Pts were censored at the time of the last follow up when data on the end of treatment were missing. For pts on active treatment, data cutoff was February 7, 2024. We identified N=22 pt who had confirmed sequential TKI regimens. Specific HER2 TKIs, order of the regimen use, and time on treatment are summarized below. The data show persistence of benefit for a second TKI use, with 64% of pts staying on a second TKI regimen for >6 months. In this small subset, tucatinib after any TKI or after prior tucatinib showed clinical benefit.Table: 207PN1st TKITime on treatment2nd TKITime on treatment7Tucatinib12 (1 - 24)Tucatinib11 (3 - 29)7Tucatinib8 (4 - 22)Neratinib or Lapatinib4 (1 - 9)8Neratinib or Lapatinib9 (1 - 16)Tucatinib20 (2 - 36)22Any TKI10 (1 - 24)Any TKI12 (1 - 36)N – number of pts; time on treatment is presented as median (range) in months. Open table in a new tab N – number of pts; time on treatment is presented as median (range) in months. These data support using HER2 TKI regimens in sequence and merit further exploration. Ongoing studies of HER2 TKIs that allow for prior TKIs (NCT05230810, NCT05458674, and others) will help gain further insights. Detailed clinical characteristics of our study will be presented at the ESMO Breast 2024.