Long-term efficacy of traditional Chinese medicine combined with chemotherapy for advanced non-small cell lung cancer: a systematic review and meta-analysis of reconstructed individual patient data over 3 years

INTRODUCTION: To evaluate the 3-year efficacy of combining traditional Chinese medicine with chemotherapy in the treatment of advanced non-small cell lung cancer, taking into account time-dependent survival effects. METHODS: A systematic review and meta-analysis was conducted following PRISMA guidelines, including randomized controlled trials and observational studies that compared chemotherapy plus traditional Chinese medicine with chemotherapy alone. Individual patient data were reconstructed from Kaplan-Meier curves. For the primary endpoints of overall survival and progression-free survival, one-stage analyses employed frailty Cox models when the proportional hazards assumption held; otherwise, Royston-Parmar models incorporating time-varying effects were used. Restricted mean survival time over 0-36 months was estimated, and a two-stage random-effects model was applied for sensitivity analysis. RESULTS: Eighteen studies (12 RCTs and 6 cohort studies) were included, with individual patient data reconstructed from 15 overall survival and 7 progression-free survival curves. The proportional hazards assumption was violated for overall survival; time-varying modeling revealed significantly better overall survival with chemotherapy plus traditional Chinese medicine therapy, with a 3-year restricted mean survival time difference of 4.149 months. In the personalized treatment subgroup, CT + TCM showed a pronounced early survival benefit, a similar benefit was observed in the fixed-regimen subgroup. For progression-free survival, combination therapy significantly improved it (HR = 0.85, 95% CI 0.77-0.93, P < 0.001), corresponding to a restricted mean survival time difference of 1.582 months. In the fixed-regimen subgroup, CT + TCM significantly improved PFS (HR = 0.85, 95% CI 0.77-0.94, P < 0.05), while in the personalized TCM subgroup the PFS benefit was not statistically significant (HR = 0.85, 95% CI 0.67-1.07, P = 0.17). CONCLUSION: The addition of traditional Chinese medicine to chemotherapy is associated with improved overall and progression-free survival in advanced non-small cell lung cancer, although the overall survival benefit diminishes over time. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ Identifier CRD420261280359.