For a study, researchers sought to examine the combined efficacy results from a phase Ib regorafenib plus nivolumab (REGONIVO) study and a phase II lenvatinib plus pembrolizumab (LENPEM) trial in advanced gastric cancer (AGC) with or without liver metastases (REGONIVO plus LENPEM cohort). Additionally, they looked into the effectiveness of anti-PD-1 monotherapies (anti-PD-1 monotherapy cohort). Using multiplex IHC, the immune microenvironments of original gastric tumors and liver metastases were also contrasted. In the REGONIVO plus LENPEM cohort with a median follow-up of 14.0 months, the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) for patients with liver metastases were, respectively, 46%, 7.8 months, and 15.6 months, compared to 69%, 6.9 months, and 15.5 months for those without. At a median follow-up of 27.6 months in the anti-PD-1 monotherapy cohort, patients with liver metastases had ORR, mPFS, and mOS of 9%, 1.4 months, and 6.4 months, respectively, compared to those without, who had ORR, 2.3 months, and 9.0 months. Compared to primary gastric tumors, liver metastases had fewer CD8+ T cells and more immune-suppressive cells, such as tumor-associated macrophages and regulatory T cells. Despite a more immunosuppressive tumor microenvironment in liver metastases, anti-PD-1 antibodies in combination with regorafenib or lenvatinib for AGC demonstrated a positive anticancer effect with a longer follow-up.
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