Pan-Cancer Analysis Identifies Liver Metastases as Negative Predictive Factor for Immune Checkpoint Inhibitors Treatment Outcome

Abstract

This study aimed to investigate the predictive value of liver metastases (LM) in patients with various advanced cancers received immune-checkpoint inhibitors (ICIs). First, clinical and survival data from a published cohort of 1,661 patients who received ICIs therapy were downloaded and analyzed. Second, a retrospective review of 182 patients with advanced non-small-cell lung cancer (NSCLC) who received PD-1/PD-L1 monotherapy was identified. Third, a meta-analysis of published trials was performed to explore the impact of LM on the efficacy of anti-PD-1/PD-L1 based therapy in advanced lung cancers. Pan-cancer analysis revealed that patients with LM had significantly shorter overall survival (OS) than those without LM (10 vs. 20 months; P < 0.0001). Subgroup analysis showed that the presence of LM was associated with markedly shorter OS than those without LM in ICI monotherapy group (P < 0.0001), but it did not reach the statistical significance in ICI-based combination therapy (P = 0.0815). In NSCLC, the presence of LM was associated with significantly inferior treatment outcomes in both pan-cancer and real-world cohort. Interestingly, ICI-based monotherapy and combination therapy could simultaneously prolong progression-free survival (PFS) and OS than chemotherapy in patients without LM. However, ICI-based monotherapy could not prolong PFS than chemotherapy in patients with LM while ICI-based combination therapy could dramatically prolong both PFS and OS. Together, these findings suggested that the presence of LM was the negative predictive factor in cancer patients received ICIs monotherapy, especially in NSCLC. ICI-based combination therapy might overcome the intrinsic resistance of LM to ICIs while the optimal combinatorial strategies remain under further investigation.