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A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study

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To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L.

Materials and methods

We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L–T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed.


One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1–43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%).


The combination of L–T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L–T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

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The authors thank the patients, their families, the nurses, and the investigators who participated in this study. The authors acknowledge Miguel Sampayo for his advice on the statistical analysis.

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Correspondence to A. Llombart-Cussac.

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Conflict of interest

This work was supported by GlaxoSmithKline plc (GSK) through a contract with Medica Scientia Innovation Research (MedSIR), an academic research organization focused on independent clinical research development. Joaquín Gavilá: Roche, Novartis, Celgene (H, SAB); César Augusto Rodríguez Sánchez: Roche, Novartis, Celgene, Eisai, AstraZeneca (H, SAB); Javier Cortés: Roche, Celgene (C/A, H), Eisai, Novartis (H); Antonio Llombart-Cussac: Roche, GlaxoSmithKline, Novartis, Celgene, Eisai, AstraZeneca (H, SAB), GlaxoSmithKline, Sanofi, Puma Biotechnology (RF); all remaining authors have declared no financial relationships. (C/A) Consulting/advisory relationship; (RF) research funding; (E) employment; (ET) expert testimony; (H) honoraria received; (OI) ownership interests; (IP) intellectual property rights/inventor/patent holder; (SAB) scientific advisory board.

Ethical approval

The protocol of this trial and informed consent were approved by the ethics committee of each participating hospital and the study has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was classified by the Spanish Agency of Medicines and Health Products.

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Written informed consent was obtained from all individual participants included in the study.

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Gavilá, J., De La Haba, J., Bermejo, B. et al. A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study. Clin Transl Oncol 22, 420–428 (2020).

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