Lapatinib and HER2 status: results of a meta-analysis of randomized phase III trials in metastatic breast cancer.

Background: In vitro studies have shown that lapatinib is most active in HER2 over-expressing tumors, but also has activity in cell lines over-expressing HER1. Consequently, clinical testing of lapatinib has been carried out in both HER2-positive and HER2-negative patients. Here we evaluate the clinical efficacy of lapatinib in HER2-positive and HER2-negative patients.

Methods: A published data meta-analysis of randomized trials that evaluated the efficacy of combining lapatinib with chemo- or endocrine therapy in patients with metastatic breast cancer was undertaken. Hazard ratios (HR) were extracted for progression free survival (PFS) and overall survival, while odds ratios were extracted for disease stabilization, serious adverse events (SAEs) and need for discontinuation. Pooled estimates were computed using inverse-variance and random-effect modeling.

Results: Three randomized controlled trials with a total of 2264 patients met the inclusion criteria. Meta-analysis demonstrated the HR for PFS with lapatinib was 0.69 in patients with HER2-positive disease, while there was no improvement in PFS (HR=0.98, 95% CI 0.80-1.19) for treatment of HER2-negative breast cancer. Similarly, overall survival was improved in HER2-positive patients (HR 0.76, 95% CI 0.60-0.96), but not in HER2-negative patients (HR 0.89, 95% CI 0.65-1.21). Patients on lapatinib were 64% more likely to develop a SAE and 2.3 times more likely to discontinue therapy due to toxicity.

Conclusion: Clinical benefit from treatment with lapatinib is limited to patients with HER2-positive breast cancer. Outside of the clinical trial setting, lapatinib should not be administered to women with HER2-negative disease because it causes increased toxicity without improving disease outcome.