Abstract 207P
Background
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.
Methods
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.
Results
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: 207P
| N | 1st TKI | Time on treatment | 2nd TKI | Time on treatment |
| 7 | Tucatinib | 12 (1 - 24) | Tucatinib | 11 (3 - 29) |
| 7 | Tucatinib | 8 (4 - 22) | Neratinib or Lapatinib | 4 (1 - 9) |
| 8 | Neratinib or Lapatinib | 9 (1 - 16) | Tucatinib | 20 (2 - 36) |
| 22 | Any TKI | 10 (1 - 24) | Any TKI | 12 (1 - 36) |
N – number of pts; time on treatment is presented as median (range) in months.
Conclusions
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.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
E. Shagisultanova: Financial Interests, Personal, Advisory Board, Advisory Board on CDK4/6 inhibitors, October 2019: Novartis; Financial Interests, Institutional, Funding, Funding for investigator initiated clinical trial: Novartis, Seagen, Pfizer; Financial Interests, Institutional, Invited Speaker, Site PI on clinical trial: Lilly. J.R. Diamond: Financial Interests, Institutional, Other, Consultant: OnKure Therapeutics; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Other, stock options: OnKure Therapeutics; Financial Interests, Institutional, Invited Speaker, PI of clinical trial at my institution with payments to my institution: HutchMed, Gilead, Merck, Cosmo, Adlai Nortye, Takeda, Seattle Genetics, BMS. P. Kabos: Financial Interests, Institutional, Principal Investigator: Radius Health, Lilly, Pfizer, AstraZeneca, Sanofi, Genentech, Angiochem; Financial Interests, Institutional, Other, Patent "Signatures in cell-free DNA to detect disease, track treatment response and inform treatment decisions": Patent / Intellectual Property. V.F. Borges: Financial Interests, Personal, Other, Funding to me paid for other KOL meetings/consultation/Ad board faculty: Seagen; Financial Interests, Personal, Advisory Board, Funds paid to me through my institution for KOL consultation/Ad Boards: AstraZeneca; Financial Interests, Personal, Other, Funding paid to me through my institution for KOL/consulting: Gilead; Financial Interests, Personal, Invited Speaker, Funds provided to me for travel to ESMO Breast 2024 to present data on an ongoing clinical trial: Olema; Financial Interests, Personal and Institutional, Invited Speaker, Steering committee Chair for Her2Climb-02 and also research support for clinical trials paid to my institution: Seagen; Financial Interests, Institutional, Invited Speaker, Research Support paid to my institution for clinical trials: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Research support paid to my institution for clinical trials: Gilead; Financial Interests, Institutional, Invited Speaker, Research support to my institution for clinical trial: OncoSec, Olema, Agendia. All other authors have declared no conflicts of interest.