Efficacy and safety of subcutaneous versus intravenous administration of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis

Objective The aim was to evaluate the differences in pharmacokinetics, clinical efficacy, and safety between subcutaneous (s.c.) and intravenous (i.v.) administration of PD-1/PD-L1 inhibitors in the treatment of solid tumors, and to explore the development history and future prospects of s.c. administration of PD-1/PD-L1 inhibitors. Methods PubMed, Embase, and The Cochrane Library were searched for relevant studies from inception to October 10, 2025. Systematic reviews and meta-analyses were used to compare the pharmacokinetics, efficacy, and safety of s.c. and i.v. PD-1/PD-L1 inhibitors in the treatment of solid tumors. Review Manager 5.4.1 was used to analyze the data. Primary outcomes and endpoints included serum drug concentration、overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AE). Results This systematic review and meta-analysis included three randomized controlled trials with a total of 1243 patients (746 received s.c. administration, and 497 received i.v. administration). Compared to the i.v. administration, there were no significant differences in drug concentration, OS [HR = 0.86; 95% CI (0.68, 1.08); P = 0.19], PFS [HR = 1.06; 95% CI (0.92, 1.23); P = 0.42], or ORR [RR = 1.18; 95% CI (0.97, 1.43); P = 0.09] for the s.c. administration of PD-1/PD-L1 inhibitors. Regarding AE, arthralgia was more commonly associated with s.c. administration, whereas i.v. administration resulted in a higher incidence of injection site reactions. Conclusion The pharmacokinetics of s.c.PD-1/PD-L1 inhibitors for the treatment of solid tumors are similar to those of i.v. administration, and no significant differences were found in efficacy and safety analyses; This finding supports s.c. administration as a viable and complementary alternative to traditional i.v. delivery. Systematic Review Registration https://www.crd.york.ac.uk/prospero , identifier CRD420251161810.