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

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.

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.

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).

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.