BACKGROUND: The efficacy and tolerability of the epidermal growth factor receptor/human epidermal growth factor receptor type 2 (HER2) tyrosine kinase inhibitor lapatinib in refractory metastatic breast cancer were assessed. PATIENTS AND METHODS: In a phase II, open-label study, patients with previously treated HER2-positive (n = 140) or HER2-negative (n = 89) metastatic breast cancer received once-daily oral lapatinib 1500 mg/day. RESULTS: Most (76%) patients had received four or more lines of prior therapy. The response rate in the HER2-positive cohort was 4.3% by investigator assessment and 1.4% by independent assessment. Both assessments established that approximately 6% of HER2-positive patients derived clinical benefit from lapatinib, being progression free for >/=6 months. No objective tumor responses occurred in the HER2-negative cohort. Independent review assessments of median time to progression and median progression-free survival were similar in the HER2-positive and HER2-negative cohorts (9.1 and 7.6 weeks, respectively). All responders exhibited HER2 overexpression (3+ by immunohistochemistry), and five of six responders were HER2 amplified by FISH. Lapatinib-related adverse events, including diarrhea (54%), rash (30%), and nausea (24%), were primarily mild to moderate in severity. CONCLUSIONS: Lapatinib monotherapy had modest clinical activity in HER2-positive metastatic breast cancer that progressed on prior trastuzumab regimens. No apparent clinical activity was observed in chemotherapy-refractory, HER2-negative disease.
BACKGROUND: The efficacy and tolerability of the epidermal growth factor receptor/humanepidermal growth factor receptor type 2 (HER2) tyrosine kinase inhibitor lapatinib in refractory metastatic breast cancer were assessed. PATIENTS AND METHODS: In a phase II, open-label study, patients with previously treated HER2-positive (n = 140) or HER2-negative (n = 89) metastatic breast cancer received once-daily oral lapatinib 1500 mg/day. RESULTS: Most (76%) patients had received four or more lines of prior therapy. The response rate in the HER2-positive cohort was 4.3% by investigator assessment and 1.4% by independent assessment. Both assessments established that approximately 6% of HER2-positive patients derived clinical benefit from lapatinib, being progression free for >/=6 months. No objective tumor responses occurred in the HER2-negative cohort. Independent review assessments of median time to progression and median progression-free survival were similar in the HER2-positive and HER2-negative cohorts (9.1 and 7.6 weeks, respectively). All responders exhibited HER2 overexpression (3+ by immunohistochemistry), and five of six responders were HER2 amplified by FISH. Lapatinib-related adverse events, including diarrhea (54%), rash (30%), and nausea (24%), were primarily mild to moderate in severity. CONCLUSIONS:Lapatinib monotherapy had modest clinical activity in HER2-positive metastatic breast cancer that progressed on prior trastuzumab regimens. No apparent clinical activity was observed in chemotherapy-refractory, HER2-negative disease.
Authors: Thomas E Delea; Carol Hawkes; Mayur M Amonkar; Konstantinos Lykopoulos; Stephen R D Johnston Journal: Breast Care (Basel) Date: 2013-12 Impact factor: 2.860
Authors: Hiroko Masuda; Dongwei Zhang; Chandra Bartholomeusz; Hiroyoshi Doihara; Gabriel N Hortobagyi; Naoto T Ueno Journal: Breast Cancer Res Treat Date: 2012-10-17 Impact factor: 4.872
Authors: M Toi; H Iwata; Y Fujiwara; Y Ito; S Nakamura; Y Tokuda; T Taguchi; Y Rai; K Aogi; T Arai; J Watanabe; T Wakamatsu; K Katsura; C E Ellis; R C Gagnon; K E Allen; Y Sasaki; S Takashima Journal: Br J Cancer Date: 2009-10-20 Impact factor: 7.640