Pathologic response in resectable non-small cell lung cancer: a systematic literature review and meta-analysis.

BACKGROUND:Surrogate endpoints for overall survival (OS) in patients with resectable non-small cell lung cancer (NSCLC) receiving neoadjuvant therapy are needed to provide earlier treatment outcomes indicators and accelerate drug approval. This study's main objectives were to investigate the association between pathologic complete response (pCR), major pathologic response (MPR), event-free survival (EFS) and OS, and to determine whether treatment effects on pCR and EFS correlate with treatment effects on OS. METHODS:A comprehensive systematic literature review was conducted to identify neoadjuvant studies in resectable NSCLC. Analysis at patient-level using frequentist and Bayesian random-effects (HR for OS/EFS by pCR/MPR status, yes vs no) and at trial-level using weighted least-squares regressions (HR for OS/EFS vs pCR by treatment arm) were performed. RESULTS:In both meta-analyses, pCR yielded favorable OS compared to no-pCR (frequentist, 20 studies and 6,530 patients: 0.49, 95% CI: 0.42, 0.57; Bayesian, 19 studies and 5,988 patients: 0.48, 95% PI: 0.43, 0.55) and similarly for MPR (frequentist, 12 studies and 1,193 patients: 0.36, 95% CI: 0.29, 0.44; Bayesian, 11 studies and 1,018 patients: 0.33, 95% PI: 0.26, 0.42). Across subgroups, estimates consistently showed better OS/EFS in pCR/MPR compared to no-pCR/no-MPR. Trial-level analyses showed a moderate to strong correlation between EFS and OS hazard ratios (R2 = 0.7159), but did not show a correlation between treatment effects on pCR and OS/EFS. CONCLUSION:There was a strong and consistent association between pathologic response and survival and moderate to strong correlation between EFS and OS following neoadjuvant therapy for patients with resectable NSCLC.