Local Consolidative Therapy Versus Systemic Therapy Alone for Metastatic Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Abstract

The role of local consolidative therapy (LCT) for metastatic cancers most likely varies by the particular cancer type. We therefore performed a systematic review with a comparative meta-analysis of LCT versus systemic therapy alone, specifically for metastatic non-small cell lung cancer (mNSCLC). Article eligibility for this Preferred Reporting Items for Systematic Reviews and Meta-Analyses/Population, Intervention, Comparison, Outcomes and Design-guided systematic review was histologic confirmation of mNSCLC, comparison of LCT (irradiation/surgery) versus lack thereof in a randomized or propensity-matched retrospective manner, and sufficient quantitative data examining progression-free survival (PFS), overall survival (OS), and/or adverse events (AEs). Both polymetastatic and oligometastatic disease (OMD) were allowed, but not oligoprogressive/oligorecurrent disease. Statistics used the Mantel-Haenszel fixed-effect or random-effect model depending on the heterogeneity (I2). From 7 articles, 346 patients received LCT and 347 received systemic therapy alone. With LCT, the hazard ratio (HR) for PFS in all patients was 0.37 (95% confidence interval, 0.25-0.55; P=.01), and for OMD it was 0.30 (0.24-0.38; P < .001). For OS, the HRs were 0.53 (0.45-0.62; P < .001) in all patients, and 0.41 (0.33-0.52; P < .001) in patients with OMD. The findings remained significant when stratifying by epidermal growth factor receptor status (HRs for PFS/OS: 0.29/0.44 for mutants and 0.31/0.39 for wild-type, respectively, P < .001 for all) and study type (HRs for PFS/OS: 0.40/0.52 for randomized and 0.33/0.41 for retrospective, respectively, P < .05 for all). LCT was not associated with a higher rate of grade ≥3 AEs (odds ratio, 1.28; 95% confidence interval, 0.81-2.05; P=.29). Meta-analyzing the available data shows that LCT may improve the PFS and OS of mNSCLC without increasing the risk of high-grade AEs. However, further data on polymetastatic mNSCLC are required, and these conclusions cannot be extrapolated to other (non-mNSCLC) histologies. Although many existing/ongoing trials of LCT for OMD commonly comprise mixed-histology populations, focusing on the interaction between specific tumor biology and systemic agents is required to enhance the clarity and applicability of these trials.