Cetuximab monotherapy in patients with advanced non-small cell lung cancer after prior epidermal growth factor receptor tyrosine kinase inhibitor therapy.

Abstract

INTRODUCTION:

Therapeutic agents directed against the epidermal growth factor receptor (EGFR) signaling pathway have been effective in the treatment of non-small cell lung cancer (NSCLC). Cetuximab is a monoclonal antibody against the EGFR receptor with antitumor activity in NSCLC. This study evaluated the efficacy of cetuximab monotherapy after prior treatment with an oral EGFR tyrosine kinase inhibitor (TKI).

METHODS:

Eligible patients had stage IIIB, IV, or recurrent NSCLC with progression on the oral EGFR TKIs gefitinib or erlotinib. Cetuximab was administered intravenously at 400 mg/m on day 1 and then 250 mg/m weekly until disease progression or unacceptable toxicity. The primary end point was response rate.

RESULTS:

Eighteen patients were enrolled. Patients were heavily pretreated with chemotherapy and TKIs (average number of treatments = 4.2). The response rate was 0/18 (0%), and 28% of patients had confirmed stable disease. Median progression-free survival was 1.8 months (95% confidence interval, 1.6-5.4 months), and median overall survival was 7.5 months (95% confidence interval, 2.2-19 months). Three patients harbored activating EGFR mutations, and one of them had stable disease for nearly 6 months on cetuximab. Common toxicities were mild and included fatigue, skin rash, and nausea/vomiting. Two patients developed interstitial lung disease, life threatening in one case.

CONCLUSIONS:

Cetuximab monotherapy administered after prior EGFR TKI treatment in patients with advanced NSCLC does not yield clinical responses.

• Authors: Joel W Neal, Rebecca S Heist, Panos Fidias, Jennifer S Temel, Mark Huberman, J Paul Marcoux, Alona Muzikansky, Thomas J Lynch, Lecia V Sequist
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 5 Issue 11 Pg. 1855-8 (Nov 2010) ISSN: 1556-1380 [Electronic] United States
• PMID: 20975380 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Protein Kinase Inhibitors
• EGFR protein, human
• ErbB Receptors
• Cetuximab

Topics

• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cetuximab
• Drug Resistance, Neoplasm (drug effects)
• ErbB Receptors (antagonists & inhibitors, genetics)
• Female
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Mutation (genetics)
• Neoplasm Recurrence, Local (diagnosis, drug therapy)
• Neoplasm Staging
• Protein Kinase Inhibitors (therapeutic use)
• Remission Induction
• Salvage Therapy
• Survival Rate
• Treatment Outcome