Factors affecting efficacy and safety of add-on combination chemotherapy for non-small-cell lung cancer: a literature-based pooled analysis of randomized controlled trials.

Background: Several clinical trials of chemotherapy for non-small-cell lung cancer (NSCLC) have been conducted to date. However, these studies have not been effective at identifying category 1 recommended strategies for systemic chemotherapy according to the National Comprehensive Cancer Network clinical practice guidelines.

Purpose And Method: To investigate the factors that influence the efficacy and safety of add-on combination chemotherapy for NSCLC based on published reports, we searched the PubMed and EMBASE for reports of randomized, controlled trials that compared efficacy and safety between groups with and without the use of add-on drugs to base chemotherapy in patients with NSCLC. For all the selected articles, we systematically retrieved and assessed the full published report.

Results: Of the 753 citations yielded by the electronic search, 82 comparison pairs from 76 articles were selected. The logistic regression analysis showed the second- or third-line treatment for target patients (Line2_3), dose modification of the base drug(s) in the investigational arm, characteristics of the add-on drug, and the number of total combination drugs that had negative coefficients, and the percent of patients with performance status 2 who had positive coefficients for efficacy. For safety, Line2_3, and the percent of female patients had positive coefficient.

Conclusions: The present results indicate that the following points are important when investigating new regimen for add-on combination chemotherapy: (1) the number of total combination drugs should be reduced if at all possible; (2) an add-on drug should be noncytotoxic and should not necessitate dose modification (reduction) of the base drug(s).