ONS Connect - November 2008 - (Page 25)

NEWTrEATmENTS,NEWHOPE New Technique Monitors Patients With NSCLC [By Deborah McBride, RN, MSN, CPON ®, Contributing Editor] lthough progress has been limited and the prognosis for patients with advanced non-small cell lung cancer (NSCLC) remains grim, recent research has promised therapeutic results based on the increasing understanding of basic cancer biology. An example of how basic cancer research is being used clinically is a recent study using a new molecular analysis technique to monitor patients with NSCLC. The new approach uses the pathway of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as gefitinib and erlotinib. These drugs inhibit the EGFR pathway by binding to the intracellular tyrosine kinase domain. The researchers found that a minority of patients have activating mutations, resulting in a high rate of response and prolonged survival. Tumors with EGFR mutations have a dramatic response to these drugs but quickly develop resistance when a sec- A ondary EGFR mutation occurs that inhibits the binding of tyrosine kinase inhibitors to the receptor sites. Therefore, the ability to characterize the EGFR gene can help refine treatment for patients with NSCLC by identifying which patients are most likely to benefit from treatment with EGFR inhibitors, to monitor treatment and to monitor changes in tumor genotypes and drug resistance. By focusing on specific oncogenic pathways that are activated in a particular tumor, rather than on the tumor’s location or histology features, researchers can identify the patients who are likely to respond to specific drugs. Minimally invasive procedures such as needle aspiration biopsies do not provide sufficient material for analysis and are not sampled regularly enough to see changes in genetic mutations associated with drug resistance. For patients with lung cancer, this has been a barrier to creating new therapies. The new study describes a novel technique that tests for EGFR mutations in circulating cancer cells by using a microfluidic device containing thousands of tiny posts covered with antibodies against the epithelial cell adhesion molecule EpCAM. This technique is a potential alternative to invasive biopsies as a source of cancer cells for genomic studies and monitoring changes during therapy. As blood samples pass through the posts at a specific rate, tumor cells adhere to the EpCAM antibodies. Using this technique, investigators captured cancer cells in blood samples from 27 patients with NSCLC (23 with EGFR mutations and 4 with no mutations). Genotyping of circulating tumor cells identified the expected mutations in 11 of 12 patients (92%). In addition, analysis of circulating tumor cells from patients with EGFR mutations who had been treated with tyrosine kinase inhibitors showed the presence of the mutation, which is associated with drug resistance. The presence of the mutation in biopsies correlated with shorter progression-free survival (7.7 versus 16.5 months). Serial analysis of the circulating tumor cells showed that a reduction of the captured cells was associated with tumor response and an increase in the captured cells was associated with tumor progression. This new technology may help not only to guide initial therapy but also to monitor treatment to understand why a particular therapy is not working. If the technique allows for detection and isolation of circulating tumor cells, it may be able to be used to identify cells from other tumor types and for molecular analysis of other pathways. Further testing and refinement as well as larger clinical trials are required to determine if this technique is a new diagnostic tool for patients. ✱ Maheswaran, S., Sequist, L.V., Nagrath, S., Ulkus, L., Brannigan, B., Collura, C.V., et al. (2008) Detection of mutations in EGFR in circulating lung-cancer cells. New England Journal of Medicine, 359(4), 366–377. Contributing Editor Deborah McBride, RN, MSN, CPON ®, is a nurse at the Kaiser Permanente Oakland Medical Center and a faculty member at Samuel Merritt College in Oakland, CA. November 2008 ONS CONNECT 25

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ONS Connect - November 2008 Contents Editor's Note Just In Lean on Me You Tell Us A Year in the Life-- Month Eleven Put Evidence Into Practice to Manage Caregiver Strain and Burden Web Connect Capitol Connection Caregiver Care New Technique Monitors Patients with NSCLC Calendar of Events Working for You Staying on Top

ONS Connect - November 2008

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