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Early phase II trials showed an encouraging activity for bevacizumab in combination with cytotoxic agents such as fluoropyrimidines, platinum derivatives, irinotecan and taxanes in metastatic GEA, with an overall response rate (ORR) in the range of 42-74%, a median progression-free survival (PFS) of 6-12 months and a median OS of 10.8-17.9 months ( Furthermore, despite ramucirumab having demonstrated its clinical activity in monotherapy or combined with paclitaxel in the second-line setting, the results of 3 randomized trials, including 2 phase II and one phase III, in the front-line treatment of GEA were surprisingly disappointing ( Ziv-aflibercept is a recombinant fusion protein that functions as a decoy receptor to bind VEGF-A, VEGF-B, and PIGF with a high affinity ( Sunitinib is a multikinase inhibitor targeting multiple RTKs, including VEGFR1-3, PDGFR, KIT, RET, colony-stimulating factor 1 and FLT3 ( Similarly, other multikinase inhibitors, such as Sorafenib and Pazopanib, showed modest activity in the treatment of advanced GEA (6569) ( Table 2 )

doi: 10.1001/archinte.159.18.2129 10 PendergrastTBrownASunnquistMJantkeRNewtonJLStrandEBet al

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