What is the optimal management of potentially resectable stage III-N2 NSCLC? Results of a fixed-effects network meta-analysis and economic modelling.

Introduction: There is a critical need to understand the optimal treatment regimen in patients with potentially resectable stage III-N2 nonsmall cell lung cancer (NSCLC). Methods: A systematic review of randomised controlled trials was carried out using a literature search including the CDSR, CENTRAL, DARE, HTA, EMBASE and MEDLINE bibliographic databases. Selected trials were used to perform a Bayesian fixed-effects network meta-analysis and economic modelling of treatment regimens relevant to current-day treatment options: chemotherapy plus surgery (CS), chemotherapy plus radiotherapy (CR) and chemoradiotherapy followed by surgery (CRS). Findings: Six trials were prioritised for evidence synthesis. The fixed-effects network meta-analyses demonstrated an improvement in disease-free survival (DFS) for CRS versus CS and CRS versus CR of 0.34 years (95% CI 0.02-0.65) and 0.32 years (95% CI 0.05-0.58) respectively, over a 5-year period. No evidence of effect was observed in overall survival although point estimates favoured CRS. The probabilities that CRS had a greater mean survival time and greater probability of being alive than the reference treatment of CR at 5 years were 89% and 86% respectively. Survival outcomes for CR and CS were essentially equivalent. The economic model calculated that CRS and CS had incremental cost-effectiveness ratios of £19 000/quality-adjusted life-year (QALY) and £78 000/QALY compared to CR. The probability that CRS generated more QALYs than CR and CS was 94%. Interpretation: CRS provides an extended time in a disease-free state leading to improved cost-effectiveness over CR and CS in potentially resectable stage III-N2 NSCLC.