Predictors of Survival to Immunotherapy and Chemoimmunotherapy in Non-Small Cell Lung Cancer: A Meta-Analysis.

BACKGROUND many patients with non-small cell lung cancer (NSCLC) derive poor benefit from immunotherapy (IO). For some of them, adding chemotherapy (CT) can improve the outcomes, but the reliability of PD-L1 expression as the only biomarker to distinguish these patients is unsatisfactory. We sought to detect clinicopathological and molecular predictive factors of survival that might be added to PD-L1 expression in the selection of patients that should receive IO alone or chemoimmunotherapy (CIT). METHODS We conducted a systematic search of randomized controlled clinical trials (RCT) investigating IO, alone or plus CT, versus CT alone in treatment-naïve advanced NSCLC patients. Meta-analyses and meta-regression analyses were performed to investigate IO alone versus CT, CIT versus CT, and IO alone versus CIT. RESULTS 14367 patients with advanced NSCLC across 25 RCT were included. Squamous histology, male sex, current/former smoker status, PD-L1 expression ≥50%, and high tumor mutational burden (TMB) correlated with improved survival with IO alone compared to CT. Conversely, female sex, no smoking history, negative PD-L1 expression, and low TMB correlated with unsatisfactory outcomes with IO alone versus CT, but not with CIT versus CT. CIT improved survival versus IO alone in female patients, never smokers, in those having a PD-L1 expression ≥1% (but not with PD-L1 ≥50%) or a low TMB, and in patients with central nervous system metastasis. CONCLUSION these findings suggest some clinicopathological and molecular features that, added to PD-L1 expression, could help in the selection of the most appropriate first-line IO-based treatment for advanced NSCLC patients.