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Considerations for Second-Line Therapy of Non-Small Cell Lung Cancer

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Key Words. Pemetrexed • Erlotinib • Docetaxel • Chemotherapy • Treatment selection

Correspondence: Correspondence: Thomas E. Stinchcombe, M.D., Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 3009 Old Clinic Building CB 7305, Chapel Hill, North Carolina 27599-7305, USA. Telephone: 919-966-4431; Fax: 919-966-6735; e-mail: Thomas_Stinchcombe{at}med.unc.edu

Disclosure: T.E.S. and M.A.S. have a financial interest in Lilly Oncology and Genentech. T.E.S. has received research funding from Eli Lilly and Company, Bristol Myers-Squibb, and Abraxis Bioscience, and has been part of a speakers bureau for Genentech and Eli Lilly and Company. M.A.S. has received research funding from Eli Lilly and Company, Genentech, Sanofi-Aventis, and Astra-Zeneca, and has been part of a speakers bureau for Eli Lilly and Company, Genentech, and Sanofi-Aventis.

For patients with advanced non-small cell lung cancer and a good functional status, platinum-based first-line chemotherapy improves quality of life, reduces disease-related symptoms, and improves survival. The addition of bevacizumab to carboplatin and paclitaxel in the first-line setting has been shown to produce a higher response rate and longer progression-free survival and overall survival times than with carboplatin and paclitaxel. Despite these therapies, all patients inevitably experience disease progression. There are currently three agents approved for treating patients who progress after one prior regimen: docetaxel, pemetrexed, and erlotinib. Erlotinib is also indicated for patients who progress after two prior regimens. These agents appear to have similar efficacies in terms of response and overall survival, but have significantly different toxicity profiles. Currently, the choice of agent depends on a number of factors, including the patient's comorbidities, toxicity from previous treatments, the risk for neutropenia, smoking history, and patient preference. A better understanding of prognostic factors in the second-line setting may allow clinicians to better select patients for second-line therapy, and lead to better-designed second-line trials. Patients with a good performance status in second-line trials have a median survival duration of approximately 9 months, and may receive two second-line therapies during the course of their treatment. Several new agents have shown activity in phase II trials, and may be integrated into second-line therapy as single agents or in combination with current agents in the future.

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