Efficacy comparison of immune treating strategies for NSCLC patients with negative PD-L1 expression

Background We intended to compare and grade the proposed immune treating strategies for non-small cell lung cancer (NSCLC) with negative Programmed Cell Death Ligand 1(PD-L1).Methods We compared the efficacy of single immune checkpoint inhibitor (ICI), single ICI plus chemotherapy, and doublet ICIs with chemotherapy alone, as well as single ICI plus radiotherapy with single ICI for negative PD-L1 (<1%) NSCLC patients. Hazard Ratio (HR) and 95% confidence interval (CI) of progression-free survival (PFS) and overall survival (OS) were used as outcomes.Results We included 23 randomized control trials with 4665 patients. Compared with chemotherapy alone, single ICI, single ICI plus chemotherapy and doublet ICIs all showed a better OS (0.84 [0.71, 0.99] ; 0.77 [0.69, 0.85] ; 0.64 [0.53, 0.77])), while single ICI plus chemotherapy and doublet ICIs showed a better PFS (0.68 [0.61, 0.75] ; 0.69 [0.56, 0.85]). Additionally, single ICI plus radiotherapy obtained a greater pooled PFS (0.49 [0.28–0.87]) than single ICI.Conclusions Both single ICI plus chemotherapy and doublet ICIs were probably better treatment decisions than chemotherapy alone for negative PD-L1 NSCLC patients. Also, single ICI plus radiotherapy carved out a new strategy.