Is fourth-line chemotherapy routine practice in advanced non-small cell lung cancer?

Background: Despite advances in palliative chemotherapy, patients with advanced non-small cell lung cancer (NSCLC) eventually experience disease progression during or after completion of first-line chemotherapy, which requires salvage therapy. Second- or third-line therapy in selected patients is recommended in the current guidelines. Although fourth-line therapy is often performed in daily practice in some countries, there are few reports about the clinical benefits of fourth-line therapy. Patients and methods: A retrospective review was conducted on 383 patients who underwent at least first-line palliative chemotherapy for advanced NSCLC (stage IV or stage IIIB/recurrent disease unsuitable for definitive local therapy). Overall survival (OS) and clinicopathological characteristics were analyzed according to the lines of chemotherapy as well as for all study patients. Results: The median OS for all patients after the initiation of first-line therapy was 11 months. The median OS for patients who received fourth- or further-line therapy (77 patients) was longer than that of patients who received third- or lesser-line therapy (27 versus 9 months, p < 0.0001). In multivariate analysis, fourth- or further-line therapy was independently associated with favorable OS (hazard ratio: 0.44,95% confidence interval: 0.34-0.57,p < 0.0001) along with recurrent disease, female, age <70 years, and ECOG performance status (PS) 0 or 1. Median OS after the start of fourth-line therapy was 9 months. Good PS (ECOG PS 0, 1) at the initiation of fourth-line therapy (10 versus 2 months, p < 0.0001) and disease control (10 versus 7 months, p = 0.011) after first-line therapy were associated with favorable OS in univariate analysis, while poor PS (ECOG PS >= 2) was an independent prognostic factor for poor outcome (p < 0.0001). Conclusion: The present study suggests that advanced NSCLC patients with good PS after progression from third-line therapy could be considered as reasonable candidates for fourth-line therapy in clinical practice. (C) 2014 Elsevier Ireland Ltd. All rights reserved.