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Chicago, IL—Taxane-based chemotherapy combined with lapatinib results in shorter progression-free survival (PFS) than with trastuzumab as first-line treatment for patients with HER2+ metastatic breast cancer, according to an interim analysis of an open-label phase 3 randomized study1 presented here at the 2012 Annual Meeting of the American Society of Clinical Oncology.

Based on this interim analysis, data from the 21-country study, sponsored by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG MA.31) in collaboration with GlaxoSmithKline (GSK EGF 108919),2 were released on May 7, 2012, and investigators, patients, and regulatory bodies informed of these results, said lead study author Karen A. Gelmon, MD, of the British Columbia Cancer Agency-Vancouver Cancer Centre, Vancouver, BC, Canada.

Lapatinib is a potent, oral selective, reversible, inhibitor of EGFR (ErbB1) and HER2 (ErbB2) receptor tyrosine kinases previously approved by the Food and Drug Administration and other regulatory agencies for patients with refractory HER2+ advanced breast cancer.1,3 This approval was based on results of a randomized phase 3 trial in women with HER2+ metastatic breast cancer with tumor progression following trastuzumab therapy that showed superior time to progression for lapatinib in combination with capecitabine vs capecitabine alone,4 the U.S. Food and Drug Administration approved the use of lapatinib in combination with capecitabine for the treatment of advanced or metastatic breast cancer in patients whose tumors overexpress HER2 and who have received prior therapy, including an anthracycline, a taxane, and trastuzumab.5

Two phase 3 randomized trials in which lapatinib was combined with paclitaxel3,6 for the first-line treatment of patients with HER2+ metastatic breast cancer have demonstrated improved efficacy; however, lapatinib had not been directly compared to trastuzumab in the first-line metastatic setting, Dr. Gelmon noted.

The newly presented trial compared paclitaxel 80mg/m2 IV once weekly 3 weeks out of 4 or docetaxel 75mg/m2 IV 3 times weekly in combination with lapatinib 1,250mg orally daily or trastuzumab 2mg/kg IV once weekly or 6mg/kg IV three times weekly after a loading dose. They then continued treatment with lapatinib 1,500mg/day or trastuzumab 6 mg/kg IV based on randomly assigned group. Patients continued treatment until disease progression; Stratification was by prior (neo)adjuvant HER2 therapy, prior (neo)adjuvant taxane-based chemotherapy, planned taxane-based chemotherapy (paclitaxel vs docetaxel), and liver metastases.