Systemic therapy beyond first-line in advanced gastric cancer: An overview of the main randomized clinical trials

- Progressive gastric cancer patients may benefit from a second-line therapy.
- Monochemotherapy (both irinotecan and taxanes) is superior to BSC.
- Novel targeted agents such as ramucirumab and apatinib are really promising.
- Ramucirumab is the first targeted drug approved by FDA and EMA in second-line.
- Future investigation should provide stronger predictive markers to targeted therapy.

Following progression on first-line platinum and fluoropyrimidine-based chemotherapy, prognosis for advanced gastric cancer patients is extremely poor. Thus, new and effective treatments are required. Based on positive results of recent randomized controlled trials, second-line monochemotherapies with either irinotecan or taxanes confer a median overall survival of approximately 5 months in gastro-esophageal and gastric adenocarcinoma. Combination of weekly paclitaxel and ramucirumab, a novel anti-angiogenic VEGFR2 antibody, pushes the overall survival up to over 9.5 months, whereas apatinib, a novel oral VEGFR2 tyrosine kinase inhibitor, seems to be promising in heavily pretreated patients. In contrast, the role of EGFR/HER2 and mTOR inhibitors is controversial. Studies are heterogeneous for tumor population, geographical areas, quality of life assessment, type of first-line therapy and response to that, making clinical practice application of the trial results difficult. Furthermore, sustainability is challenging due to high cost of novel biotherapies.