Rationale for a phase II trial of pertuzumab, a HER-2 dimerization inhibitor, in patients with non–small cell lung cancer

摘要: Background and Rationale: In non–small cell lung cancer (NSCLC) HER-2 gene amplification and 3+ staining by immunohistochemistry are present in only 2% to 5% of the tumors. Therefore, relatively few patients with lung cancer are likely to benefit from treatment with trastuzumab, the humanized monoclonal antibody that is effective in the 20% of patients with breast cancer and HER-2 gene amplification and/or 3+ staining by immunohistochemistry. Pertuzumab (rhuMAb 2C4), a humanized HER2 antibody, represents a new class of targeted therapeutics that inhibit dimerization of HER2 with ligand-activated EGFR (HER1), HER3, and HER-4. Pertuzumab can have antitumor activity in patients with HER-2 present on the tumor without gene amplification or 3+ staining by immunohistochemistry. Preclinical xenograft studies have shown efficacy of pertuzumab in treating NSCLC. Therefore, a trial was …