IS1-3 - Perspective of Systemic Chemotherapy for Gastric Cancer in Europe

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Randomized trials showed that cytotoxic treatment prolongs survival and provides improved symptom control in advanced gastric cancer. Combination chemotherapy (CTx) with cisplatin and 5-FU is a preferred 1st-line CTx in Europe, but oxaliplatin has shown equivalent efficacy compared with cisplatin. Oral fluoropyrimidines, especially S-1 and capecitabine, can substitute for 5-FU. Modern doublet regimens are preferred in the majority of patients on the basis of a balanced benefit-risk ratio. In selected, fit and compliant patients, especially those with high tumor burden or potential secondary resectability, a third drug may be added as triple CTx led to higher responses rates and enhanced efficacy.Current study concepts evaluate the feasibility and efficacy of de-escalation protocols and maintenance treatment with less toxic drugs, e.g. S-1 monotherapy. This concept is currently studied following response induced by intensive induction CTx.The comprehension of tumor biology is increasing. In HER2 positive gastric cancer, the addition of the anti-HER2 monoclonal antibody trastuzumab to cisplatin and FU has prolonged survival. Novel anti-HER2-directed drugs like pertuzumab are being explored. More genetic alterations have been defined in subgroups of gastric cancer, like MET or FGFR amplification. Its role for therapeutic targeting remains to be elucidated.2nd-line CTx with single agents has now become a proven treatment option. Alternatively, anti-angiogenic treatment with ramucirumab has been published with positive data and will be made available.In conclusion, combination CTx is a European 1st-line standard for treating advanced gastric cancer. Molecularly targeted agents are further explored, preferably on the backbone of chemotherapy doublets. For further-line treatment, monotherapy with cytotoxics and - in the future - ramucirumab are the preferred options.