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Future Oncol. 2013 Mar;9(3):327-45. doi: 10.2217/fon.13.6.

Moving towards molecular-guided treatments: erlotinib and clinical outcomes in non-small-cell lung cancer patients.

Author information

1
Medical Oncology Unit of Respiratory Tract & Sarcomas, New Drugs Development Division, European Institute of Oncology, Milan, Italy. c.santarpia@hotmail.com

Abstract

Erlotinib is an orally administered small-molecule inhibitor of EGF receptor (EGFR) tyrosine kinase that is approved for the treatment of non-small-cell lung cancer (NSCLC) and pancreatic cancer. Erlotinib was first approved for the treatment of unselected NSCLC patients with advanced disease after failure of at least one prior chemotherapy regimen, and it was subsequently demonstrated to also confer a significant clinical benefit as maintenance therapy after first-line platinum-based chemotherapy. In all clinical studies, erlotinib treatment was associated with a good safety profile. Activating mutations in the EGFR gene have emerged as the strongest predictive marker of response to tyrosine kinase inhibitors, erlotinib and gefitinib, independently of other clinical and molecular features. Results from recently published, randomized Phase III trials showed that first-line erlotinib significantly prolongs progression-free survival in patients with advanced EGFR mutation-positive NSCLC with favorable tolerability, compared with standard chemotherapy. EGFR mutation testing is a crucial factor in the decision-making process regarding the most appropriate initial treatment option for patients. Specific molecular alterations in crucial genes have been discovered and associated with resistance to erlotinib, limiting its efficacy. New targeted agents and combined-treatment strategies are now under evaluation in clinical trials of NSCLC patients following progression to tyrosine kinase inhibitors.

PMID:
23469969
DOI:
10.2217/fon.13.6
[Indexed for MEDLINE]

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