Molecularly Targeted Therapies for Gastric Cancer. State of the Art.

Abstract

Simple SummaryDespite 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. We conducted a literature search for randomized trials investigating novel molecular agents as compared to conventional chemotherapy. The outcomes were patients’ survival and the rates of tumor response and of severe adverse effects (SAE). Although we did not find an increase of SAE, the survival benefits of novel molecular therapies available to date for advanced and metastatic gastric cancer were rather unclear, mostly due to inaccurate patient selection, particularly concerning oncogene amplification and copy number.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. We examined the efficacy and safety of novel drugs recently investigated. PubMed, Embase and Cochrane Library were searched for phase III randomized controlled trials published from January 2016 to December 2020. Patients in the experimental arm received molecular therapy with or without conventional chemotherapy, while those in the control arm had conventional chemotherapy alone. The primary outcomes were overall and progression-free survival. The secondary outcomes were the rate of tumor response, severe adverse effects, and quality of life. Eight studies with a total of 4223 enrolled patients were included. The overall and progression-free survival of molecular and conventional therapy were comparable. Most of these trials did not find a significant difference in tumor response rate and in the number of severe adverse effects and related deaths between the experimental and control arms. 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.