Phase II Study of Lapatinib in Combination With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Clinical Outcomes and Predictive Value of Early [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003)

Abstract

Purpose Lapatinib plus trastuzumab improves outcomes relative to lapatinib alone in heavily pretreated, human epidermal growth factor receptor 2–positive metastatic breast cancer (MBC). We tested the combination in the earlier-line setting and explored the predictive value of [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) for clinical outcomes. Patients and Methods Two cohorts were enrolled (cohort 1: no prior trastuzumab for MBC and ≥ 1 year from adjuvant trastuzumab, if given; cohort 2: one to two lines of chemotherapy including trastuzumab for MBC and/or recurrence < 1 year from adjuvant trastuzumab). The primary end point was objective response rate by RECIST v1.0; secondary end points included clinical benefit rate (complete response plus partial response plus stable disease ≥ 24 weeks) and progression-free survival. [18F]FDG-PET scans were acquired at baseline, week 1, and week 8. Associations between metabolic response and clinical outcomes were explored. Results Eighty-seven patients were registered (85 were evaluable for efficacy). The confirmed objective response rate was 50.0% (95% CI, 33.8% to 66.2%) in cohort 1 and 22.2% (95% CI, 11.3% to 37.3%) in cohort 2. Clinical benefit rate was 57.5% (95% CI, 40.9% to 73.0%) in cohort 1 and 40.0% (95% CI, 25.7% to 55.7%) in cohort 2. Median progression-free survival was 7.4 and 5.3 months, respectively. Lack of week-1 [18F]FDG-PET/computed tomography ([18F]FDG-PET/CT) response was associated with failure to achieve an objective response by RECIST (negative predictive value, 91% [95% CI, 74% to 100%] for cohort 1 and 91% [95% CI, 79% to 100%] for cohort 2). Conclusion Early use of lapatinib and trastuzumab is active in human epidermal growth factor receptor 2–positive MBC. Week-1 [18F]FDG-PET/CT may allow selection of patients who can be treated with targeted regimens and spared the toxicity of chemotherapy.