Alexander R Siebenhüner1,2, Sara De Dosso3,4, Daniel Helbling5, Christoforos Astaras6, Petr Szturz7, Peter Moosmann8, Stefanie Pederiva9, Thomas Winder5, Philippe Von Burg10, Markus Borner11. 1. Clinic for Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland. 2. Cantonal Hospital Schaffhausen, Schaffhausen, Switzerland. 3. Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland. 4. Università della Svizzera Italiana, Lugano, Switzerland. 5. OnkoZentrum Zurich, Zurich, Switzerland. 6. University Hospital of Geneva (HUG), Geneva, Switzerland. 7. Lausanne University Hospital (CHUV), Lausanne, Switzerland. 8. Cantonal Hospital Aarau, Aarau, Switzerland. 9. Cantonal Hospital Baden, Baden, Switzerland. 10. Buergerspital Solothurn, Solothurn, Switzerland. 11. ONCOCARE AG Oncology Centre in the Klinik Engeried, Bern, Switzerland.
Abstract
BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. SUMMARY: Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, Epstein-Barr virus expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and <70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. Key Message: In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.
BACKGROUND:Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. SUMMARY: Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, Epstein-Barr virus expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and <70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. Key Message: In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.
Authors: Xiaomei Miao; Hongying Wu; Yan Liu; Shu Zhang; Chaohui Li; Jie Hao Journal: Evid Based Complement Alternat Med Date: 2022-07-30 Impact factor: 2.650
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