Safety and efficacy of subcutaneous versus intravenous administration of PD (L)1 inhibitors in patients with solid tumors: A systematic review and meta-analysis.

Abstract

e14590 Background: Intravenous (IV) administration of Programmed Cell Death 1/Ligand 1 (PD (L)1) inhibitors is the standard of care for the treatment of various solid tumors. Subcutaneous (SC) formulations were developed as an alternative to improve healthcare efficiency, cost-effectiveness, and patient preferences. However, limited evidence exists comparing the safety and efficacy of PD(L)1 inhibitors SC versus IV administration. This systematic review and meta-analysis evaluated their comparative efficacy and safety in patients with solid tumors. Methods: We systematically searched PubMed, Embase, and Cochrane Library for studies comparing SC versus IV administration of PD (L) 1 inhibitors in patients with solid tumors. Outcomes of interest included progression-free survival (PFS), Objective Response Rate (ORR), Treatment Emergent adverse events (TEAEs), Treatment related adverse events (TRAEs) and Treatment emergent anti-drug antibodies (TEADAs). We pooled risk ratios (RR) with 95% confidence intervals (CI). Statistical analysis was performed using random-effects model in Review Manager 5.4.1 for studies comparing SC versus IV, and single-arm proportional meta-analysis was conducted in R software 4.4.2 to summarize safety for SC PD(L)1 inhibitors. Results: Ten studies involving 1,401 patients were included, with three studies (two RCTs and one non-RCT) analyzed for comparative outcomes and ten (two RCTs and eight non-RCTs) for SC safety. PD(L)1 inhibitors included nivolumab, atezolizumab, sansalimab and envafolimab. Patients ranged in age from 20 to 93 years and primarily had advanced or metastatic clear cell renal cell carcinoma (ccRCC) or non-small cell lung cancer (NSCLC). No significant differences were observed between SC and IV administration in PFS (HR 1.07; 95% CI 0.90–1.28) or ORR (RR 1.27; 95% CI 0.94–1.71). Safety outcomes revealed no distinctions in TEAEs (RR 1.01; 95% CI 0.98–1.05), TRAEs (RR 0.96; 95% CI 0.86–1.08), or TEADAs (RR 1.92; 95% CI 0.96–3.83) between SC versus IV administration. A sensitivity analysis with only RCTs was performed and showed similar results. The single-arm analysis included 1,005 SC-treated patients. TEAEs were reported in 91.22% (95% CI 86.75–94.92) of patients, with grade 3–4 TEAEs in 24.96% (95% CI 18.50–32.00). TRAEs occurred in 63.37% (95% CI 53.19–73.00) of patients, with grade 3–4 TRAEs in 8.94% (95% CI 6.06–12.25). TEADAs were present in 22.06% (95% CI 11.84-34.24) patients. Conclusions: SC and IV administration of PD(L)1 inhibitors showed comparable efficacy and safety, supporting SC as a viable alternative to IV in solid tumors.