Advances In Non-Small Cell Lung Cancer



The landscape of oncology has become very exciting over the last three years for Non Small Cell lung cancer (NSCLC). With the event of genomic research, new therapeutic targets have been identified and more targets continue to be identified.

The importance of identifying specific tumor targets is to “personalize” care for patients. One of the most established targets for NSCLC (adenocarcinoma) is the Epidermal Growth Factor Receptor (EGFR) mutation. This mutation is found in 20% of patients tested. The EGFR mutation is highly predictive of sensitivity to EGFR inhibitor therapies like Tyrosine Kinase Inhibitors (TKI): Iressa and Tarceva which translates in prolonged survival. These two particular drugs are oral which means convenience for the patient, TKI’s have a much different side effect profile than chemotherapeutic agents.

Another EGFR inhibitor is Erbitux, a monoclonal antibody which is given intravenously. None of the EGFR inhibitors exhibit bone marrow suppression but all give a rash which is directly related to efficacy. The newest monoclonal antibody in the EGFR positive tumors is MetMab, a humanized monoclonal antibody targeting C-MET. In combination with a TKI, MetMab improved disease free survival and overall survival in recent studies adding another novel therapeutic option.

Approximately, 5% of patients with NSCLC present with the Anaplastic Lymphoma Kinase (ALK) translocation which is a therapeutic target with a highly effective target treatment called crizotinib. Crizotinib is an oral kinase inhibitor taken twice a day with a limited side effect profile and the response to treatment is very high and prolonged resulting in survival advantage.

Twenty to 25% of patients with adenocarcinoma of the lung have been found to have the K-RAS mutation which is another target with potential for new personalized therapeutic options in the near future.

Another exciting therapeutic target common to many tumors including lung is Vascular Endothelial Growth Factor (VEGF) target for Avastin, an antiangiogenic agent with good efficacy in combination treatment with TKI’s or chemotherapy.

As far as squamous cell lung cancer, the research is still in progress but some fibroblast grown factor inhibitors currently being tested appear to have promise. We are also moving toward choosing cytotoxic agents based on specific cancer biomarkers like betatubulin, RRMI and ERCCI which would guarantee efficacy when choosing potentially toxic agents.

The therapeutic options for lung cancer patients have exploded in the last few years and will continue to broaden in the future. As a patient, ask your doctor about what is best for you.