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 [ 18 F]Fluorodeoxyglucose Positron Emission Tomography Imaging (TBCRC 003)

• Published in: Journal of clinical oncology Vol. 33; no. 24; pp. 2623 - 2631
• Main Authors: Lin, Nancy U., Guo, Hao, Yap, Jeffrey T., Mayer, Ingrid A., Falkson, Carla I., Hobday, Timothy J., Dees, E. Claire, Richardson, Andrea L., Nanda, Rita, Rimawi, Mothaffar F., Ryabin, Nicole, Najita, Julie S., Barry, William T., Arteaga, Carlos L., Wolff, Antonio C., Krop, Ian E., Winer, Eric P., Van den Abbeele, Annick D.
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 20.08.2015
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - diagnostic imaging; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cohort Studies; Female; Fluorodeoxyglucose F18; Humans; Middle Aged; Neoplasm Metastasis; ORIGINAL REPORTS; Positron-Emission Tomography - methods; Quinazolines - administration & dosage; Receptor, ErbB-2 - biosynthesis; Trastuzumab; Treatment Outcome
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2014.60.0353

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. 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. 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). 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.