Immune checkpoint inhibitors combined with HER-2 targeted therapy in HER-2 positive gastroesophageal cancer. (December 2022)

• Record Type: Journal Article
• Authors: Aisa, Adilai; Weng, Shanshan; Li, Xinyu; Zhang, Ding; Yuan, Ying
• Is Part Of: Critical reviews in oncology/hematology. Volume 180(2022)
• Publication Date: 2022-12
• Subjects: GEC Gastroesophageal cancer -- HER-2 Human epidermal growth factor receptor-2 -- PD1 / PD-L1 programmed cell death protein1/ programmed death ligand 1 -- CTLA4 cytotoxic T-lymphocyte-associated protein 4 -- Lag-3 Lymphocyte activation gene-3 -- OS overall survival -- TOGA Trastuzumab for Gastric Cancer study -- TME tumor micro-environment -- FDA food and Drug Administration -- TMB tumor mutational burden -- MSI-H microsatellite instability-high -- dMMR mismatch repair deficient -- TILs tumor- infiltrating lymphocytes -- INF-γ interferon-γ -- EBV Epstein–Barr Virus -- ADCC antibody-dependent cellular cytotoxicity -- NK Natural Killer -- TAMs tumor-associated macrophages -- BsAb bispecific antibody -- mAb monoclonal antibody -- ORR objective response rate -- DCR disease control rate -- SD stable disease -- mPFS median progression-free survival -- NGS next-generation sequencing -- AEs adverse events -- RR response rate -- ORR Overall response rate -- T-DXd Trastuzumab deruxtecan -- MMAE monomethyl auristatin E -- pCR pathologic Complete Response -- MPR major pathologic response -- CPS combined positive score -- CAFs cancer-associated fibroblasts -- TSR Tumor stromal ratio; HER-2 -- Immunotherapy -- Immune checkpoint inhibitors -- HER-2 targeted treatments -- Gastroesophageal cancer; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2022.103864
• Languages: English
• ISSNs: 1040-8428

Abstract

Abstract: GEC is one of the most common cancers and has become a significant health burden worldwide. HER-2 is a proto-oncogene, amplified or overexpressed in different tumors, and associated with a worse prognosis. Trastuzumab plus chemotherapy is the current standard treatment for advanced HER-2 positive GEC. However, it still does not benefit well all patients. HER-2 targeted therapy can up-regulate the expression of PD-1, CTL-4, and TAMs in the tumor microenvironment, strengthen the ADCC process, and enhance the efficacy of immunotherapy. While immune checkpoint inhibitors could reduce drug resistance to anti-HER-2 drugs. Moreover, immunotherapy combined with HER-2 targeted therapy in HER-2 positive GEC has shown perceptible efficacy and acceptable side effects in clinical trials and is regarded as a new therapeutic strategy for GEC. However, there remain significant challenges and requires more research to improve the survival benefit of this therapeutic approach. Graphical Abstract: HER-2-positive cancers have some special immune microenvironment, related to better respond to the immunotherapy, encouraged us to try and introduce immune checkpoint inhibitors into the treatment of HER-2-positive GEC combine with HER-2 targeted therapies and showed great potential results in clinical trials researches. ga1 Highlights: GEC is one of the top 10 common cancers and HER-2 + GEC is associated with worse prognosis. Current treatment strategies do not benefit well all HER-2 + GEC patients, so it's urgent to find new treatment options for these patients. The combination of immune checkpoint inhibitors and HER-2 targeted therapy demonstrated synergistic tumor inhibition. The combination of immune checkpoint inhibitors and HER-2 targeted therapy is efficiency and safe in clinical treatment of HER-2 + GEC.