TY - JOUR
T1 - Phase II study of lapatinib in combination with trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer
T2 - Clinical outcomes and predictive value of early [18F]fluorodeoxyglucose positron emission tomography imaging (TBCRC 003)
AU - Lin, Nancy U.
AU - Guo, Hao
AU - Yap, Jeffrey T.
AU - Mayer, Ingrid A.
AU - Falkson, Carla I.
AU - Hobday, Timothy J.
AU - Dees, E. Claire
AU - Richardson, Andrea L.
AU - Nanda, Rita
AU - Rimawi, Mothaffar F.
AU - Ryabin, Nicole
AU - Najita, Julie S.
AU - Barry, William T.
AU - Arteaga, Carlos L.
AU - Wolff, Antonio C.
AU - Krop, Ian E.
AU - Winer, Eric P.
AU - Van Den Abbeele, Annick D.
N1 - Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
PY - 2015/8/20
Y1 - 2015/8/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2014.60.0353
DO - 10.1200/JCO.2014.60.0353
M3 - Article
C2 - 26169615
AN - SCOPUS:84940517700
SN - 0732-183X
VL - 33
SP - 2623
EP - 2631
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 24
ER -