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

Purpose 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). Methods and Materials 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). Results 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). Conclusions 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. 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.