Efficacy and safety of tremelimumab plus durvalumab (STRIDE) versus durvalumab monotherapy in advanced hepatocellular carcinoma: A systematic review and meta-analysis.

e14577 Background: Durvalumab monotherapy and the STRIDE regimen (tremelimumab plus durvalumab) are approved immunotherapy options for advanced hepatocellular carcinoma (HCC). While both have shown clinical benefit, direct comparisons are limited. Methods: PubMed, Cochrane, Embase, and Scopus were searched systematically for relevant studies from inception to May 2025. Risk ratios (RR) with 95% confidence intervals (CI) were pooled for dichotomous outcomes using Mantel-Haenszel method with random effect model. Heterogeneity was assessed using I² and χ² statistics. The quality of the studies was evaluated using the Cochrane Risk of Bias 2.0 (RoB 2.0) tool. Results: Three studies with 991 patients were included. No significant difference in 18-month survival between STRIDE and durvalumab (RR = 1.18, 95% CI:0.84–1.66; I² = 72%; P = 0.33). The overall response rate favored STRIDE (RR = 1.52, 95% CI:1.03–2.24; I² = 21%; P = 0.03). Partial response and complete response rates were also higher with STRIDE but not statistically significant (PR: RR = 1.44, 95% CI:0.99–2.09; I² = 17%; P = 0.06; CR: RR = 1.95, 95% CI: 0.82–4.68; I² = 0%; P = 0.13). Regarding safety, STRIDE was associated with higher risk of any-grade adverse events and grade 3 adverse events, (RR = 1.78, 95% CI:0.98–3.14; I² = 92%; P = 0.06 and RR = 1.92, 95% CI:1.37–2.68; P = 0.0001 respectively). There was no differences in liver toxicity (ALT: RR = 1.41, 95% CI: 0.46–5.25; I² = 79%; P = 0.56; and AST: RR = 1.25, 95% CI: 0.55–2.88; I² = 64%; P = 0.59) and diarrhea incidence (RR = 1.87, 95% CI: 0.75–4.68, I² = 69%; P = 0.18) between both groups. However, treatment discontinuation due to adverse events (RR = 1.92, 95% CI: 1.07–3.46; I² = 0%; P = 0.03) were higher with STRIDE. Conclusions: STRIDE showed a significantly higher ORR than Durvalumab in advanced HCC, with comparable survival and manageable toxicity. However, further large-scale RCTs are needed to confirm these findings and establish STRIDE as a standard treatment option.