Tucatinib Plus Trastuzumab Plus Capecitabine Is Efficacious After Trastuzumab Deruxtecan Exposure in HER2-Positive MBC

The oral tyrosine kinase inhibitor tucatinib in combination with trastuzumab and capecitabine (TTC) is indicated for patients with advanced unresectable or HER2-positive metastatic breast cancer (MBC) who have received ≥1 prior anti-HER2–based regimen in the metastatic setting. This retrospective study was conducted to determine the efficacy of the TTC regimen in a subset of patients with previous trastuzumab deruxtecan (T-DXd) exposure. Results of the study were presented at the 2023 ASCO meeting.

This multicenter retrospective study was conducted in 12 French comprehensive cancer centers; inclusion criteria were patients with HER2-positive MBC who received TTC after previous T-DXd exposure. The primary end point was progression-free survival (PFS) in the total population; secondary end points included overall survival (OS) and PFS in specific subgroups, and response rate by local investigators.

A total of 101 eligible patients were identified; median age was 56 years. In the total population, patients had received a median of 5 prior lines of treatment at TTC initiation, whereas those with metastatic disease had received a median of 4 prior lines of treatment. Most patients (93%) had received previous trastuzumab emtansine; 81% of these patients had progressed on T-DXd. Median duration of prior T-DXd exposure was 8.9 months.

The majority of patients (85%) received TTC regimen as the immediate subsequent therapy to T-DXd; 37% received TTC regimen as third-line or fourth-line therapy for metastatic disease. At a median follow-up of 8.5 months, 67% of patients experienced progression of disease and TTC was discontinued. At TTC initiation, 39 patients had known brain metastases; 2 others were documented during TTC therapy.

In the total population, median PFS was 4.7 months and median OS was 13.4 months. In the subset of patients who received TTC as the immediate subsequent therapy to T-DXd, median PFS was 5.0 months and median OS was not reached. Of the 87 evaluable patients, 2% achieved a complete response, 30% achieved a partial response, 34% achieved stable disease, and 34% experienced progressive disease.

Based on the results of this large retrospective cohort, the investigators concluded that TTC treatment was efficacious in patients with HER2-positive MBC previously exposed to T-DXd.


Frenel J-S, Zeghondy J, Guerin C, et al. Efficacy of tucatinib+trastuzumab+capecitabine (TTC) after trastuzumab deruxtecan (TDXd) exposure in Her2-positive metastatic breast cancer: a French multicentre retrospective study. Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract 1014.

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