Second-line treatments in non-small cell lung cancer. A systematic review of literature and metaanalysis of randomized clinical trials.

Background: To assess the efficacy of second-line treatments in non-small cell lung cancer (NSCLC).

Methods: A systematic review of literature with metaanalysis of randomized clinical trials (RCTs) was independently performed by three authors. A primary analysis included all RCTs comparing any approach (chemotherapy or therapy with epidermal growth factor receptor [EGFR] inhibitors) with placebo; a secondary analysis included all RCTs comparing any treatment with docetaxel therapy every 3 weeks. The 1-year survival rate (SR) of the primary analysis was the primary outcome of the study; the 1-year SR of the secondary analysis, response rate (RR), and time to progression of primary and secondary analyses were the secondary end points.

Results: Fourteen RCTs met the selection criteria. The outcomes of 2,627 and 5,952 patients were analyzed in the primary and secondary analysis, respectively. A significant heterogeneity was documented in the primary analysis for 1-year SR with odd ratio [OR] = 0.763 (p = 0.029). No heterogeneity was documented for RR in the primary analysis, with OR = 0.165 (p < 0.001). A modest heterogeneity was documented in the secondary analysis for 1-year SR and RR, with 1-year SR OR = 0.924 (p = 0.122) and RR OR = 1.069 (p = 0.643).

Conclusion: Second-line treatments in NSCLC seem to improve the main outcomes better than supportive care. Docetaxel administration every 3 weeks probably remains the "gold standard" because at present the data in literature are not enough to support a greater efficacy of other alternative options. Further trials are needed to identify a clinical and biological profile that could predict the response to treatments and a criterion to select the patients to be treated with chemotherapy or EGFR inhibitors.