Alternative strategy to achieve increased overall survival and better quality of life in patients with second-line advanced non-small-cell lung cancer.

Abstract

TO THEEDITOR: Recent studies, including the article by Zer and Leighl 1 entitled “Second-Line Therapy in Non-Small-Cell Lung Cancer: The DELTA Between Different Genotypes Widens,” have suggested that chemotherapy is the best option for the treatment of patients with second-line advanced non–small-cell lung cancer (NSCLC) with wild-type (WT) epidermal growth factor receptor (EGFR). On the basis of the results of several randomized phase III clinical trials, pemetrexed, docetaxel, and erlotinib are all US Food and Drug Administration–approved therapies for use in this setting. ● The article by Zer and Leighl 1 states that the key goals of systemic therapy in advanced NSCLC are the improvement of symptoms, quality of life, and overall survival (OS) with minimal toxicity in the second-line setting in patients with WT EGFR. As part of this analysis, the authors discuss data that demonstrate the equivalence of EGFR tyrosine kinase inhibitors (TKIs) and chemotherapy in OS in nine randomized clinical trials. In contrast, further discussion centered on EGFR TKIs as inferior in patients with WT EGFR, using progression-free survival (PFS) and response from a recent meta-analysis 2 as their main argument. However, Lee et al discussed several flaws in their own comparison; most notably, several different lines of treatment were compared, the overall comparisons were not based on study randomization, and toxicity outcomes were not assessed. It should emphasized that the biology of tumor progression in a patient treated with platinum-doublet chemotherapy is different than biology of a chemotherapy-naive patient, and one cannot make the assumption that chemotherapy will be superior in a chemotherapy-treated EGFR WT patient group. Both the data from the meta-analysis 2 and from the Docetaxel and Erlotinib Lung Cancer Trial (DELTA) 3 concluded that although chemotherapy was associated with longer PFS as compared with EGFR TKI in patients with WT tumors, OS did not differ significantly between the groups. However, does PFS really address our key treatment goals for second-line treatment decisions? In this patient population, quality of life and OS should be primary end points and not PFS. Evidence for this viewpoint have previously been presented in Journal of Clinical Oncology (JCO). 4 We also point out that despite gains in PFS for patients receiving chemotherapy, the toxicity may be detrimental to OS. Finally, in a separate article in the same issue of JCO, Sacher et al 5 described the use of PFS as a surrogate for