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

Bruce E. Johnson, Pasi A. Jänne, Jeffrey Engelman, John Heymach, David Johnson, Glenwood Goss, Thomas Lynch

Research output: Contribution to journalArticle

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Abstract

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 dose then 420 mg every 3 weeks). Mandatory fresh tumor biopsies before treatment were obtained for biomarker analysis including HER-2 phosphorylation. Computed 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 patients with 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.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume12
Issue number14
DOIs
StatePublished - Jul 15 2006

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Dimerization
Non-Small Cell Lung Carcinoma
Gene Amplification
erbB-2 Genes
Antibodies, Monoclonal, Humanized
Immunohistochemistry
Neoplasms
Staining and Labeling
pertuzumab
Neoplasm Genes
Therapeutic Uses
Therapeutics
Heterografts
Lung Neoplasms
Biomarkers
Tomography
Phosphorylation
Breast Neoplasms
Ligands
Biopsy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rationale for a phase II trial of pertuzumab, a HER-2 dimerization inhibitor, in patients with non-small cell lung cancer. / Johnson, Bruce E.; Jänne, Pasi A.; Engelman, Jeffrey; Heymach, John; Johnson, David; Goss, Glenwood; Lynch, Thomas.

In: Clinical Cancer Research, Vol. 12, No. 14, 15.07.2006.

Research output: Contribution to journalArticle

Johnson, Bruce E. ; Jänne, Pasi A. ; Engelman, Jeffrey ; Heymach, John ; Johnson, David ; Goss, Glenwood ; Lynch, Thomas. / Rationale for a phase II trial of pertuzumab, a HER-2 dimerization inhibitor, in patients with non-small cell lung cancer. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 14.
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abstract = "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 dose then 420 mg every 3 weeks). Mandatory fresh tumor biopsies before treatment were obtained for biomarker analysis including HER-2 phosphorylation. Computed 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 patients with 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.",
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AU - Lynch, Thomas

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