Efficacy and safety of low-dose versus standard-dose immune checkpoint inhibitor as monotherapy in patients with solid tumors: A meta-analysis and systematic review.

188 Background: Immunotherapy is a novel anti-cancer therapy with different mechanisms compared with chemotherapy. Several studies have reported that low dose of immune checkpoint inhibitors (ICIs) is effective. However, it is unknown whether the efficacy of low-dose immunotherapy is inferior to that of standard dose immunotherapy. We aimed to compare the existing randomized clinical trials on the efficacy of immunotherapy at low dose and standard dose as a single agent for patients with solid tumors. Methods: We searched PubMed, EMBASE, and the Cochrane Library for randomized clinical trials with the clinical outcomes of low dose and standard dose of programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor as monotherapy until November 30, 2023. The low dose is defined as lower than the dose approved by FDA. The hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) and disease control rate (DCR) were collected. The Stata 15.0 software was used to analyze the data. Results: Twenty-two studies with 3226 patients with five ICIs for 22 solid tumors were included. There is no difference in OS (HR 1.12, 95% CI = 0.97-1.31; p > 0.05), ORR (Odds ratio (OR) 0.92, 95% CI = 0.76-1.11; p > 0.05) and DCR (OR 0.83, 95% CI = 0.65-1.06; p > 0.05) for patients with low dose and standard dose of PD-1/PD-L1 inhibitors. Conclusions: Our results suggested that PD-1/PD-L1 inhibitor as monotherapy with a low dose may be as effective as standard dose for patients with solid tumors. The regular dose-response relationship may not be appropriate for ICIs. Further work is needed to explore the optimal dose of ICIs based on the comprehensive consideration of efficacy, safety, and economic assessment.