Annals of Oncology Advance Access published online on February 17, 2008
Annals of Oncology, doi:10.1093/annonc/mdm601
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A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer
1 Medical Oncology, Dana Farber Cancer Institute, Boston, MA
2 Oncology, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN
3 Oncology, Memorial Cancer Institute, Hollywood, FL
4 Medicine Development Center Oncology, GlaxoSmithKline, Collegeville, PA
5 Oncology, Duke University Medical Center, Durham, NC, USA
* Correspondence to: Dr H. J. Burstein, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. Tel: +1-617-632-2624; Fax: +1-617-632-1930; E-mail: hburstein{at}partners.org
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 
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.
breast cancer, EGFR, ErbB2, targeted therapy, tyrosine kinase inhibitor, trastuzumab
Received for publication December 13, 2007. Accepted for publication December 17, 2007.