Early Lapatinib and Trastuzumab Active in HER2-Positive Metastatic Breast Cancer


Key Points

  • Earlier use of lapatinib plus trastuzumab was active in metastatic breast cancer.
  • Lack of early [18F]FDG-PET/CT response was predictive of lack of objective response.

Lapatinib plus trastuzumab improves outcomes vs lapatinib in heavily pretreated HER2-positive metastatic breast cancer. In the phase II TBCRC 003 study reported in the Journal of Clinical Oncology, Lin et al found that earlier use of lapatinib plus trastuzumab was active in HER2-positive metastatic breast cancer and that early [18F]fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography (CT) may be used to predict lack of response.

Study Details

The study included two cohorts of patients with zero to two prior lines of treatment for metastatic breast cancer who were treated with lapatinib (Tykerb) plus trastuzumab (Herceptin): Cohort 1 patients (n = 40) had received no prior trastuzumab for metastatic breast cancer and had received adjuvant trastuzumab ≥ 1 year prior to study (or no adjuvant trastuzumab); cohort 2 patients (n = 45) had received one or two lines of chemotherapy including trastuzumab for metastatic breast cancer or had recurrence < 1 year from adjuvant trastuzumab. [18F]FDG-PET/CT scans were performed at baseline, week 1, and week 8.

Response Rates and [18F]FDG-PET/CT Response

Lapatinib plus trastuzumab treatment was associated with confirmed objective response rates of 50.0% (95% confidence interval [CI] = 33.8%–66.2%) in cohort 1 and 22.2% (95% CI = 11.3%–37.3%) in cohort 2, clinical benefit rates of 57.5% and 40.0%, and median progression-free survival of 7.4 and 5.3 months.

Absence of [18F]FDG-PET/CT response at week 1was associated with failure to achieve an objective response, with negative predictive values of 91% (95% CI =74%–100%) in cohort 1 and 91% (95% CI = 79%–100%) in cohort 2.

The investigators concluded: “Early use of lapatinib and trastuzumab is active in human epidermal growth factor receptor 2–positive [metastatic breast cancer]. Week-1 [18F]FDG-PET/CT may allow selection of patients who can be treated with targeted regimens and spared the toxicity of chemotherapy.”

Nancy U. Lin, MD, of the Susan F. Smith Center for Women’s Cancers, Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article. 

The study was supported by the AVON Foundation, Breast Cancer Research Foundation, Susan G. Komen for the Cure, GlaxoSmithKline, National Cancer Institute Specialized Program of Research Excellence at Dana-Farber/Harvard Cancer Center, The Nancy and Randy Berry Junior Faculty Fund, Dunkin’ Donuts Rising Star Program, and CJL Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.