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

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 undertaken for patients with relapsed NSCLC. Materials and Methods: Subjects with advanced or recurrent NSCLC treated previously, with chemotherapy were treated with pertuzumab (840 mg i.v. loading close,then 420 mg every 3,weeks). Mandatory fresh tumor biopsies before treatment were obtained for biomarker analysis including HER-2 phosohorylation Computed for tomography scans were obtained,every two cycles to assess tumor response. Tumor response (response evaluation criteria in solid, tumors criteria) was the primary end point. Results: As reported in a previous abstract, none of the 33 patients with NSCLC and evaluable disease had a response to the treatment. Conclusions: Pertuzumab has an appropriate rationale for therapeutic use in patients with NSCLC. A phase II trial in with patients NSCLC has completed enrollment,and the details of the trial will be presented in a future publication. This article will review-the preclinical rationale for undertaking a study of pertuzumab for patients with relapsed NSCLC.