In the most recent update, investigators conducted a literature search for all relevant randomized trials published since 2002, looking specifically for treatment strategies that improved overall survival. Drugs that were found to only improve progression-free survival were evaluated in light of their toxicity and quality-of-life benefits. Several new drugs have entered the market, so it was important to take a fresh look at our first- and second-line therapies. One of the most important additions to first-line treatment for stage IV NSCLC has been the arrival of bevacizumab, which can be used in conjunction with carboplatin-paclitaxel. There have also been new arrivals on the second-line therapy, including pemetrexed and erlotinib. In addition to existing therapies, these new drugs have been evaluated and ranked according to a number of treatment scenarios and the likely benefits that they can confer to patients.

According to the evidence, these newer drugs appear to have made an impact on treatment decisions. Clinicians should recognize that it’s important to tailor treatments based on individual characteristics of patients. For example, physical age should no longer be factored into treatment decisions. Instead, patients’ physiological age and performance status are more appropriate benchmarks for deciding on treatments. Additionally, race and genetic makeup appear to impact treatment strategies.

 Genes Matter

A new aspect of the 2009 ASCO guideline update is the evaluation of genetic biomarkers, which may affect how patients will respond to a particular agent. While there are several biomarkers with evidence supporting an impact on disease progression, none are currently as well-characterized as mutations in the epidermal growth factor receptor (EGFR). When patients have known EGFR mutations, treatment should be tailored in order to attain greater efficacy. For example, first-line treatment with gefitinib is preferred for patients with a positive-EGFR mutation. For those with an unknown or negative mutation status, cytotoxic chemotherapy is recommended. It’s important to note, however, that research is still ongoing. Biomarker testing is not yet recommended as a routine method of treatment selection. When more investigations become available on routine biomarker testing, it is hoped that this information will further improve survival.

“ASCO’s updated guidelines can be used to help improve outcomes based on evidence that is currently available.”

 Looking Forward

There are now more options than ever for NSCLC patients who experience disease recurrence after first-line treatments. The treatment armamentarium for advanced NSCLC is rapidly evolving, and pharmaceutical companies and developers are continuing to seek out new solutions in this field. As testing for biomarkers becomes less invasive and more routine, it may drive changes in how clinicians treat the disease. Ultimately, this information may lead to more tailored treatment regimens based on individual characteristics of tumors. ASCO’s updated guidelines can be used to help improve outcomes based on evidence that is currently available. Clinicians should remember to discuss treatment plans with patients in great detail to avoid concerns about treatments, side effects, and costs. They can also use ASCO’s decision guides to assist decision making for patients with advanced NSCLC.

References

Azzoli CG, Baker S Jr, Temin S, et al. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2009;27:6251-6266. Available at: http://jco.ascopubs.org/cgi/reprint/JCO.2009.23.5622v2.

Morita S, Okamato I. Combined survival analysis of prospective clinical trials of gefinitib for non-small cell lung cancer with EGFR mutations. Clin Cancer Res. 2009;15:4493-4498.

NSCLC Meta-Analyses Collaborative Group: Chemotherapy in addition to supportive care improves survival in advanced non–small-cell lung cancer: A systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol 2008;26:4617-4625.

Spiro SG, Rudd RM, Souhami RL, et al: Chemotherapy versus supportive care in advanced nonsmall cell lung cancer: Improved survival without detriment to quality of life. Thorax. 2004;59:828-836.

For decision guides on the treatment of non-small-cell lung cancer from the American Society for Clinical Oncology, go to http://www.asco.org/guidelines/nsclc.