Influence of Taxanes on Treatment Sequence in Gastric Cancer.

BACKGROUND: Adenocarcinoma of the stomach and esophagogastric junction (EGJ) remains a tumor entity with a poor prognosis. While meaningful advances have been made in the treatment of other solid tumors in the past years, numerous phase III studies in gastric cancer have had negative outcomes. Successes of targeted therapies so far include the -introduction of trastuzumab in the first-line treatment of HER2-positive gastric cancer, and second-line anti-angiogenic treatment with the anti-VEGF-2 receptor antibody ramucirumab. Taxanes have become established in the perioperative setting and in second-line treatment and have set new standards. However, evidence for improved overall survival in the first-line treatment of advanced gastric cancer with taxanes is not convincing.

METHODOLOGY: Expert consensus discussion on the scientific and clinical evidence for sequential systemic treatment for advanced gastric and EGJ cancer, taking into account data clinical outcomes from randomized controlled phase II and phase III trials.

SUMMARY: In first-line treatment of advanced gastric cancer, taxanes in combination with a platinum- and 5-fluorouracil-based regimen are generally not recommended because they lack a survival benefit and confer high toxicity. However, taxanes in first-line can be a treatment option for patients presenting with high tumor burden and strong pressure to achieve remission. Since the publication of several positive studies in second- and third-line therapy, sequential therapy is playing an increasingly important role in metastatic gastric and EGJ cancer. Key Message: Standard of care for the first-line treatment of gastric cancer is a platinum-fluoropyrimidine chemotherapy doublet combination. The standard of care after failure of platinum-based first-line therapy is ramucirumab in combination with paclitaxel. Data supporting this combination after previous taxane therapy are not yet available.