Response Rate and Survival at Key Timepoints With PD-1 Blockade vs Chemotherapy in PD-L1 Subgroups: Meta-Analysis of Metastatic NSCLC Trials.

Background: Expression of programmed cell death ligand 1 (PD-L1) on tumor cells with or without immune cells is widely reported in clinical trials of programmed cell death receptor 1 (PD-1) blockade in metastatic non-small cell lung cancer. Various cutpoints have been studied. Methods: We performed a systematic search of MEDLINE, EMBASE, and conference proceedings up to December 2019 for randomized and nonrandomized clinical trials of anti-PD-1 or anti-PD-L1 monotherapy in metastatic non-small cell lung cancer. We retrieved data on objective response rate (ORR), 1-year and 2-year progression-free survival (PFS), and 2-year and 3-year overall survival (OS) in various PD-L1 subgroups. Results were pooled and analyzed based on different cutpoints, with nonrandomized comparisons made with pooled chemotherapy outcomes. Results: A total of 9810 patients in 27 studies were included. In treatment-naïve patients, benefits with PD-1 blockade over chemotherapy were seen in ORR in patients having PD-L1 50% or greater, in 2-year OS for PD-L1 1% or greater, and in 1-year PFS, 2-year PFS, and 3-year OS for unselected patients. First-line PD-1 blockade compared with chemotherapy demonstrated higher ORR, 2-year PFS, and 3-year OS if PD-L1 was 50% or greater; lower ORR, higher 2-year PFS, and similar 3-year OS if PD-L1 was 1%-49%; and lower ORR, similar 1-year PFS, and lower 2-year OS if PD-L1 was less than 1%. In previously treated patients, PD-1 blockade demonstrated similar or superior outcomes to chemotherapy in all PD-L1 subgroups. Conclusions: PD-L1 should guide the choice of PD-1 blockade vs chemotherapy in treatment-naïve patients. In previously treated patients, PD-1 blockade provides a favorable outcome profile to chemotherapy in all PD-L1 subgroups.