Many phase III trials failed to demonstrate a survival benefit from the addition of molecular therapy to conventional chemotherapy for advanced and metastatic gastric cancer, and only three agents were approved by the FDA. Despite recent advances in surgical techniques and in anticancer drugs, and the adoption of perioperative treatments mostly based on conventional chemotherapy, the prognosis of advanced and metastatic gastric cancer remains poor. In the last decade, the addition of molecular therapy did not show any significant survival advantage, and the first reports available documented an increase of the rate of severe adverse effects and related mortality. The survival benefits of molecular therapies available to date for advanced and metastatic gastric cancer are rather unclear, mostly due to inaccurate patient selection, particularly concerning oncogene amplification and copy number.
The results showed that despite their newly documented safety, the molecular therapies available to date for advanced and metastatic gastric cancer do not present clear survival benefits. These unfavorable results are mostly related to inadequate patient selection. Targeted therapies are promising treatments for patients with locally advanced, metastatic, or recurrent gastric cancer as they are for other types of tumors. However, their clinical validation requires accurate patient selection, particularly related to driver oncogene amplification and copy number, and it should take into account preclinical models investigating cancer heterogeneity and escape mechanisms.