A phase II study of lapatinib monotherapy in chemotherapy-refractory HER2-positive and HER2-negative advanced or metastatic breast cancer
H J Burstein1, A M Storniolo, S Franco
1Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA. hburstein@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 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.
Insights
Lapatinib showed modest clinical activity in HER2-positive metastatic breast cancer, particularly in patients previously treated with trastuzumab. The drug demonstrated no significant benefit in HER2-negative breast cancer patients.
Area of Science:
- Oncology
- Pharmacology
- Medical Research
Background:
- Assessing lapatinib's efficacy and tolerability in patients with refractory metastatic breast cancer.
- Evaluating a tyrosine kinase inhibitor targeting epidermal growth factor receptor/human epidermal growth factor receptor type 2 (HER2).
Purpose of the Study:
- To determine the clinical activity of lapatinib in patients with previously treated HER2-positive and HER2-negative metastatic breast cancer.
- To assess the safety and tolerability profile of lapatinib in this patient population.
Main Methods:
- A phase II, open-label study involving 140 HER2-positive and 89 HER2-negative metastatic breast cancer patients.
- Patients received once-daily oral lapatinib at 1500 mg/day, with most having received four or more prior therapy lines.
Main Results:
- A 4.3% response rate (investigator) and 1.4% (independent) in HER2-positive patients; approximately 6% achieved clinical benefit (progression-free for ≥6 months).
- No objective tumor responses were observed in the HER2-negative cohort. Diarrhea, rash, and nausea were the most common adverse events.
- All responders showed HER2 overexpression (3+ IHC), and most were HER2 amplified (FISH).
Conclusions:
- Lapatinib monotherapy demonstrated modest clinical activity in HER2-positive metastatic breast cancer progressing on trastuzumab-based regimens.
- No significant clinical activity was observed with lapatinib in chemotherapy-refractory, HER2-negative metastatic breast cancer.
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