Safety profile of dual TIGIT and PD-L1 blockade with tiragolumab plus atezolizumab in solid tumors: a systematic review and meta-analysis of randomized controlled trials

INTRODUCTION: Dual immune-checkpoint blockade targeting T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and programmed death-ligand 1 (PD-L1) shows synergistic antitumor activity. However, its safety profile remains incompletely defined. Our systematic review and meta-analysis aim to evaluate the safety of tiragolumab in combination with atezolizumab (TA) for the treatment of solid tumors. METHODS: We conducted a comprehensive literature search up to March 2026. Eligible studies were Phase II or III randomized controlled trials (RCTs) comparing TA with atezolizumab-based regimens and reporting adverse events (AEs); pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: Five RCTs involving 1001 patients were included. TA was associated with significantly higher risks of rash (RR 1.66, 95% CI 1.16-2.37), pruritus (RR 2.28, 95% CI 1.65-3.16), and infusion-related reactions (RR 1.80, 95% CI 1.23-2.62). No significant differences were observed for gastrointestinal, hematologic, endocrine, laboratory, or high-grade AEs. Subgroup analyses of TA alone versus atezolizumab alone showed only a significantly higher rash risk (RR 3.85, 95% CI 1.40-10.53). CONCLUSIONS: TA increases rash, pruritus, and infusion-related reactions without a significant rise in severe toxicities. Limited trial numbers and clinical heterogeneity require cautious interpretation and further long-term safety evaluation.