Nancy U Lin1, Hao Guo2, Jeffrey T Yap2, Ingrid A Mayer2, Carla I Falkson2, Timothy J Hobday2, E Claire Dees2, Andrea L Richardson2, Rita Nanda2, Mothaffar F Rimawi2, Nicole Ryabin2, Julie S Najita2, William T Barry2, Carlos L Arteaga2, Antonio C Wolff2, Ian E Krop2, Eric P Winer2, Annick D Van den Abbeele2. 1. Nancy U. Lin, Hao Guo, Nicole Ryabin, Julie S. Najita, William T. Barry, Ian E. Krop, Eric P. Winer, and Annick D. Van den Abbeele, Dana-Farber Cancer Institute; Andrea L. Richardson and Annick D. Van den Abbeele, Brigham and Women's Hospital, Boston, MA; Jeffrey T. Yap, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Ingrid A. Mayer and Carlos L. Arteaga, Vanderbilt-Ingram Cancer Center, Nashville, TN; Carla I. Falkson, University of Alabama, Birmingham, AL; Timothy J. Hobday, Mayo Clinic, Rochester, MN; E. Claire Dees, University of North Carolina, Chapel Hill, NC; Rita Nanda, University of Chicago, Chicago, IL; Mothaffar F. Rimawi, Baylor College of Medicine, Houston, TX; and Antonio C. Wolff, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD. nlin@partners.org. 2. Nancy U. Lin, Hao Guo, Nicole Ryabin, Julie S. Najita, William T. Barry, Ian E. Krop, Eric P. Winer, and Annick D. Van den Abbeele, Dana-Farber Cancer Institute; Andrea L. Richardson and Annick D. Van den Abbeele, Brigham and Women's Hospital, Boston, MA; Jeffrey T. Yap, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Ingrid A. Mayer and Carlos L. Arteaga, Vanderbilt-Ingram Cancer Center, Nashville, TN; Carla I. Falkson, University of Alabama, Birmingham, AL; Timothy J. Hobday, Mayo Clinic, Rochester, MN; E. Claire Dees, University of North Carolina, Chapel Hill, NC; Rita Nanda, University of Chicago, Chicago, IL; Mothaffar F. Rimawi, Baylor College of Medicine, Houston, TX; and Antonio C. Wolff, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
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 [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]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. [(18)F]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 [(18)F]FDG-PET/computed tomography ([(18)F]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 [(18)F]FDG-PET/CT may allow selection of patients who can be treated with targeted regimens and spared the toxicity of chemotherapy.
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 [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]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. [(18)F]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 [(18)F]FDG-PET/computed tomography ([(18)F]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 [(18)F]FDG-PET/CT may allow selection of patients who can be treated with targeted regimens and spared the toxicity of chemotherapy.
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