Lapatinib activity in metastatic human epidermal growth factor receptor 2-positive breast cancers that received prior therapy with trastuzumab, pertuzumab, and/or ado-trastuzumab emtansine (T-DM1)
Lapatinib (L) is approved in combination with capecitabine or letrozole for patients with trastuzumab-resistant HER2-positive metastatic breast cancer (MBC). However, there is no efficacy data of L in patients who received prior pertuzumab (P) and ado-trastuzumab emtansine (T-DM1), now included as standard first- and second-line therapies, respectively. The goal of this study was to assess the efficacy of L in a contemporary patient population that received prior P and/or T-DM1.
We identified patients with HER2-positive MBC who received L (n = 520) between 2003 and 2017 at MD Anderson Cancer Center and selected a target cohort who received L after prior P or T-DM1 (n = 43) with the remaining included in the comparison cohort (n = 477). We evaluated outcome measures including clinical benefit rate (CBR), best tumor response (BTR), duration on L, and time to progression (TTP). Survival analyses used Kaplan–Meier statistics.
CBR was 28% (95% CI 10–32) for the target cohort and 40% (95% CI 36–45) for the comparison cohort. The median duration on L was 5 months (95% CI 3.0–9.0) in the target cohort and 6.7 months (5.9–8.0) in the comparison cohort. In both cohorts, the median time to progression (TTP) and overall survival (OS) were longer in patients with de novo metastatic disease compared to patients with disease recurrence.
L-based therapy is an active therapeutic option and remains a viable option for HER2 + MBC after prior trastuzumab, P and/or T-DM1.
KeywordsLapatinib Trastuzumab Pertuzumab T-DM1 HER2 Breast cancer Metastatic
Design/conception: LB, VV, RM. Data collection: LB, AR. Statistical analysis: KH. Data interpretation: All authors. Manuscript writing: All authors.
The database used for this work is supported by the Breast Medical Oncology departmental funds at MD Anderson Cancer Center. KR Hess was supported by the NIH/NCI under award number P30CA016672 and used the Biostatistics Resource Group shared resource.
Compliance with ethical standards
Conflict of interest
Luiz Baez-Vallecillo, Akshara S. Raghavendra, Kenneth R. Hess, Carlos H. Barcenas, and Vicente Valero report no conflict of interest relevant to this work. Stacy L. Moulder serves or has served as a consultant for Novartis, Oncothyreon, Pfizer, and Immunogenics. Debu Tripathy serves as a consultant for Novartis and Pfizer, and also receives funding from Novartis. Rashmi K. Murthy receives research funding from Cascadian therapeutics, Daiichi Sankyo, Gnentech, and Pfizer (all in research support paid to the institution).
This article does not contain any studies with human participants or animals.
This study was approved by the institutional review board at MD Anderson Cancer Center, and waivers for obtaining informed consent were granted.
- 12.Schneeweiss A et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24(9):2278–2284CrossRefGoogle Scholar
- 21.Dieras V et al (2017) Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol 18(6):732–742CrossRefGoogle Scholar
- 26.Moulder SL et al (2017) Phase I study of ONT-380, a HER2 inhibitor, in patients with HER2+-advanced solid tumors, with an expansion cohort in HER2+ metastatic breast cancer (MBC). Clin Cancer ResGoogle Scholar
- 27.Murthy R, Borges VF, Conlin A, Chaves J, Chamberlain M, Gray T, Vo A, Hamilton E (2018) Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol 19:880–888CrossRefGoogle Scholar