SRS390 - Solid organ metastasis to the liver confers immune checkpoint blockade resistance: a systematic review and meta-analysis of randomised trials

Abstract Background Metastatic disease of solid organ tumours carries poor prognosis. Curative surgery of these lesions is often futile or technically unachievable, resulting in the need for systemic treatment options to downstage the number and size of deposits. Preclinical evidence using mouse models indicates that the presence of liver metastasis confers immunotherapy resistance through global immunosuppression. We therefore aimed to assess whether the presence of liver metastasis was associated with a reduction in overall survival in patients receiving immunotherapy. Methods This systematic review and meta-analysis was conducted according to PRISMA guidelines, resulting in 4343 unique studies. Article screening and meta-extraction was conducted by 4 independent reviewers using pre-specified criteria published prospectively, limiting to randomised trials assessing the survival benefit of immunotherapy use in patients with solid organ metastatic disease, in the presence or absence of secondary liver lesions. Summary statistics are presented as forest plots for Hazard Ratios. Results 98 randomised trials including 60 688 patients were identified for analysis, 10 of which involved patients with metastatic lung cancer. Liver metastasis was associated with reduced overall survival benefit compared with standard of care (HR = 0.92, 95%c.i.:0.79–1.07 with liver metastasis versus HR = 0.78, 95%c.i.:0.72–0.85 without liver metastasis), Figure 1a/b. Discussion The findings may indicate that the presence of liver metastasis may induce immunotherapy resistance in patients with solid organ tumours but that this is primary tumour dependent. Further analyses are required utilising all available trial evidence, and radiological data to assess response using iRECIST criteria, to confirm whether this effect is generalisable across primary cancer aetiology.