Gastric Cancer: Advanced/Metastatic Disease

Gastric cancer represents today the second leading cause of cancer-related deaths: in fact, its diagnosis usually occurs in later stages due to the lack of specific and early symptoms. Palliative chemotherapy is the only therapeutic option for advanced disease, but the prognosis remains overall poor despite treatments available. According to international guidelines, a doublet or triplet fluoropyrimidine-/platinum-based chemotherapy is the standard of care for locally advanced unresectable/metastatic gastric cancer, while for HER2-positive cases, trastuzumab in combination with chemotherapy represents the treatment of choice as first line. To note, many biological agents, studied in several clinical trials, such as pertuzumab, TDM-1, cetuximab, panitumumab, onartuzumab, rilotumumab, and others, did not show benefit for this malignancy. Instead, promising results are deriving from immunotherapy with anti-PD-1 agents such as pembrolizumab and nivolumab, although we are only starting to understand the predictive factors of response to these immune checkpoint agents (e.g., MSI status and EBV status). Finally, recent positive results of TAGS trial with trifluridine/tipiracil in third-line setting pointed out the establishment of “continuum of care” concept even in this hard-to-treat disease: indeed, the presence of robust first-, second-, and even third-line therapies has greatly expanded therapeutic opportunities for GC patients nowadays, increasing quality and quantity of life. This chapter reports the most relevant clinical, molecular, and translational information about GC, leading to a more modern and multidisciplinary therapeutic approach for this awful disease.