A phase II, randomized trial using the small molecule tyrosine kinase inhibitor lapatinib as a first-line treatment in patients with FISH positive advanced or metastatic breast cancer

Abstract

3046 Background: Phase I and II studies of lapatinib, an oral small molecule inhibitor of both ErbB1 (EGFR) and ErbB2 (Her-2/neu) kinase activity, suggested activity in metastatic breast cancer in a refractory setting. The primary objective of this study was to evaluate the anti-tumor activity of two dosing regimens of lapatinib as a first-line treatment for patients with locally advanced or metastatic breast cancer, centrally tested for ErbB2 amplification by FISH. Methods: Patients were randomly assigned to receive oral lapatinib as either a single daily dose of 1500mg, or 500mg twice daily. Eligible patients had tumors which amplified the ErbB2 gene and measurable disease (RECIST). Patients were not previously treated with trastuzumab in the metastatic setting, and those with any prior therapy for advanced or metastatic disease were excluded. The primary endpoint was response rate at Week 12, after which patients could choose to remain on treatment if no signs of progressive disease were observed. Response was defined by RECIST. Final enrollment of 130 patients is planned; an interim analysis is scheduled after 40 patients reach 12 weeks of treatment. Results: As of Nov. 2004, 29 patients were enrolled. Preliminary data on the first 13 patients randomized to treatment indicated that 5/13 had stage IIIb or IIIc disease, 8/13 had stage IV disease. Eight of 13 patients had an ECOG PS score of zero at baseline. No unexpected toxicity was reported thus far. A confirmed partial response was demonstrated in 5/13 (38%) patients. An additional 6/13 patients had stable disease for at least eight weeks, and 2/13 had progressive disease. Conclusion: Lapatinib appears well tolerated and shows evidence of activity in this FISH positive first-line patient population. These data support the emerging role of small molecule tyrosine kinase inhibitors in the treatment of patients with breast cancers exhibiting ErbB2 amplification. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline