방사선의학 웹진

바로가기  >

[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.

© 2015 by American Society of Clinical Oncology.

​[Author information]

Lin NU1, Guo H2, Yap JT2, Mayer IA2, Falkson CI2, Hobday TJ2, Dees EC2, Richardson AL2, Nanda R2, Rimawi MF2, Ryabin N2, Najita JS2, Barry WT2, Arteaga CL2, Wolff AC2, Krop IE2, Winer EP2, Van den Abbeele AD2.​

1Nancy 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.

2Nancy 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.