Chemoimmunotherapy efficacy in patients with and without liver metastases: A systematic review and meta-analysis

Liver metastases have been associated with poor prognosis and potentially diminished immunotherapy benefit. Comprehensive evidence regarding whether liver involvement affects the efficacy of immune checkpoint inhibitor plus chemotherapy regimens remains incomplete.

Following PRISMA guidelines, we systematically searched five databases through May 2025 for randomized controlled trials comparing chemoimmunotherapy versus chemotherapy alone in solid tumors, with survival data stratified by liver metastasis status. We conducted random-effects meta-analyses with pre-specified subgroup analyses by tumor type, immune checkpoint inhibitor, and chemotherapy backbone. Methodological rigor was ensured through meta-regression analysis, sensitivity testing, formal interaction assessment, and systematic evaluation of publication bias.

Forty-two trials with 25,915 patients (18,830 men, 7085 women) met inclusion criteria. Within-trial interaction analyses of 30 trials per outcome yielded pooled interaction hazard ratios of 1.00 (95% CI: 0.91-1.09, p = 0.92) for overall survival (OS) and 1.04 (95% CI: 0.93-1.17, p = 0.49) for progression-free survival (PFS), with confidence intervals excluding clinically meaningful effect modification. Combination chemoimmunotherapy significantly improved survival in both groups: OS hazard ratios were 0.76 (95% CI: 0.71-0.82) in patients with liver metastases and 0.76 (95% CI: 0.73-0.79) in those without; PFS hazard ratios were 0.64 (95% CI: 0.58-0.71) and 0.59 (95% CI: 0.56-0.63), respectively.

Chemoimmunotherapy significantly improved OS and PFS in both patients with and without liver metastases. Formal interaction testing did not demonstrate statistically significant effect modification by liver metastasis status, indicating that the treatment benefit was not detectably different between groups.