Comparative efficacy and safety of PD-1/PD-L1 inhibitors versus docetaxel in the treatment of non-small cell lung cancer: a systematic review and meta-analysis.

[BACKGROUND] Non-small cell lung cancer (NSCLC) is the most prevalent histological subtype of lung cancer globally and remains a leading cause of cancer-related mortality. The advent of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors has markedly transformed advanced NSCLC treatment, providing patients with broader access to individualized treatment strategies. This study aims to systematically examine the efficacy and safety of PD-1/PD-L1 inhibitors in treating NSCLC in comparison to docetaxel.

[METHODS] PubMed, Embase, Cochrane, and Web of Science were thoroughly retrieved from inception to 2024. Data on overall survival (OS), progression-free survival (PFS) with 95% confidence intervals (CIs), pooled hazard ratios (HRs), duration of response (DOR) with 95% CIs, objective response rate (ORR) with odds ratios (ORs), as well as treatment-related adverse events (TRAEs) with relative risks (RRs), were extracted and analyzed. All data analysis was performed using Stata 18.0 software. Publication bias was examined via funnel plots and quantified utilizing Egger's and Begg's test.

[RESULTS] This meta-analysis encompassed 11 randomized controlled trials (RCTs) comprising 6,770 patients. Compared with docetaxel, PD-1/PD-L1 inhibitors notably ameliorated OS [weighted mean difference (WMD): 2.89 months, 95% CI: 2.13-3.65, P<0.001] but demonstrated no evident improvement in PFS (WMD: 0.41 months, 95% CI: -0.45 to 1.26, P<0.001). Moreover, PD-1/PD-L1 inhibitors correlated with a lowered death risk (HR 0.72, 95% CI: 0.65-0.80, P=0.005) and progression (HR 0.81, 95% CI: 0.71-0.93, P<0.001). Similarly, they displayed an evidently higher ORR than docetaxel (OR 2.67, 95% CI: 1.73-4.10, P<0.001) and were linked to a decrease in overall TRAEs as well as a substantial decrease in grade 3-4 TRAEs (RR 0.80, 95% CI: 0.76-0.84, P<0.001; RR 0.28, 95% CI: 0.22-0.36, P<0.001). Additionally, PD-1/PD-L1 inhibitors prolonged the DOR (WMD: 12.42 months, 95% CI: 8.79-16.06, P<0.001). Subgroup analyses proved that compared with low expression, high tumor proportion score (TPS) expression of PD-1/PD-L1 inhibitors conferred a greater OS benefit and effectively lowered the likelihood of death and progression, though no significant PFS prolongation was observed. Moreover, PD-1 inhibitors had a more pronounced decrease in mortality and progression risk, as well as a greater improvement in ORR, compared with PD-L1 inhibitors.

[CONCLUSIONS] Regarding OS, PFS, ORR, DOR and TRAEs outcomes, PD-1/PD-L1 inhibitors exhibit superior efficacy and safety than docetaxel in NSCLC patients. The therapeutic benefit is more pronounced in cases with high TPS expression and with PD-1 inhibitors alone.