Rita Quaresma FERREIRA, Carolina Brandão MONTEIRO, Ana Catarina DIAS, Francisca ABREU, Bogdana DARMITS, Maria João OURA, Inês ÂNGELO, Joana CABRAL, Alice FIGUEIREDO, Ricardo FERREIRA, Diogo Alpuim COSTA, Maria Teresa MARQUES, Tiago PINA-CABRAL, Filipe ARAÚJO, Sandra BENTO, Catarina Lopes FERNANDES, Mariana SANTIAGO, Bruno SILVA, Maria Alexandra MONTENEGRO, Diana Cardoso SIMÃO, Leonor FERNANDES, Sónia Duarte OLIVEIRA
European Journal of Breast Health - 2026;22(3):318-327
Objective: The HER2CLIMB trial demonstrated the benefit of tucatinib, trastuzumab and capecitabine (TTC) in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). However, it predated the clinical use of trastuzumab deruxtecan (T-DXd), leaving limited evidence for TTC after T-DXd exposure. This national multicenter study assessed the real-world effectiveness and safety of TTC in patients, including those previously treated with T-DXd. Materials and Methods: This retrospective, non-interventional study included patients with HER2-positive ABC treated with TTC across 17 centers in Portugal (October 2021-May 2025). Outcomes included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Eighty-one patients were included (median age 54 years). Of the patients, 39.5% (n = 32) had brain metastases, and 61.7% (n = 50) had prior T-DXd exposure. Median follow-up was 21.0 months; ORR and DCR were 24.4% and 64.1%, respectively. Median PFS (mPFS) was 9.0 months (m) [95% confidence interval (CI): 5.9-12.1], and median OS (mOS) was 14.0 months (m) (95% CI: 10.5-17.5). In patients previously treated with T-DXd, the median mPFS 7.0 m (95% CI: 3.6-10.4) and 13.0 m (95% CI: 9.3-16.7), respectively. Among patients with brain metastases, mPFS was 12.0 m (95% CI: 6.7-17.3) and mOS was 17.0 m (95% CI: 12.9-21.1). The most frequent all grade adverse events were fatigue (58.0%) and diarrhea (56.8%); CTCAE grade >=3 events occurred in 16.0%. Treatment discontinuation due to toxicity occurred in 7.4% of participants; there were no treatment-related deaths. Conclusion: In this national real-world cohort, TTC demonstrated clinically meaningful activity and was not associated with any new safety signals in HER2-positive ABC, including patients previously exposed to T-Dxd and those with brain metastases.
