Targeted Therapies in Advanced Gastric Cancer
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Upper Gastrointestinal Cancers (JD Berlin, Section Editor)
Targeted Therapies in Advanced Gastric Cancer Timil H. Patel, MD Michael Cecchini, MD* Address * Department of Internal Medicine (Medical Oncology), Yale School of Medicine, 333 Cedar St, PO Box 208028, New Haven, CT, 06520, USA Email: [email protected]
* Springer Science+Business Media, LLC, part of Springer Nature 2020
This article is part of the Topical Collection on Upper Gastrointestinal Cancers Keywords Gastric cancer I Molecular targeted therapy I Biomarkers I HER2 I VEGF I Immunotherapy
Opinion statement Despite a decreasing incidence in the USA, gastric cancer is highly prevalent worldwide. Furthermore, gastric cancer remains highly lethal with median survival of less than 1 year for metastatic disease. The backbone of therapy against metastatic gastric cancer remains cytotoxic chemotherapy, but recent advances in the molecular understanding of gastric cancer have renewed hope within that targeted agents can be leveraged to improve survival and reduce toxicity. For example, in patients with human epidermal growth factor-2 (HER2)-positive gastric cancer, the addition of trastuzumab to frontline chemotherapy improves survival. In the second line, oncologists can now administer a vascular endothelial growth factor (VEGF) receptor inhibitor, ramucirumab, as a single agent or in combination with chemotherapy, and the immune checkpoint inhibitor pembrolizumab is approved in multiple settings dependent on the Programmed Death Ligand 1 (PD-L1) status. For patients with metastatic disease, our approach to standard of care in the firstline setting is a 5FU/platinum doublet with trastuzumab for HER2-positive tumors. In the second-line setting, most patients receive ramucirumab + paclitaxel, but those that are MSI high receive pembrolizumab. For squamous cell carcinoma of the esophagus with high PD-L1 status (combined positive score (CPS) ≥ 10), we recommend pembrolizumab in the second line. While for PD-L1 ≥ 1% gastroesophageal adenocarcinoma, we do not recommend pembrolizumab before the third-line setting, although this may change in the near future for CPS ≥ 10. The future landscape for targeted therapy in gastric cancer is promising. Numerous clinical trials evaluating the combination immune therapy with molecularly targeted agents are generating much excitement. Moreover, genomic data from The Cancer Center Genome (TCGA) and Asian Cancer Research Group (ACRG) classifications is being used to identify molecular subtypes to enable future clinical trials to include biomarker-enriched patient populations.
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Curr. Treat. Options in Oncol.
(2020) 21:70
Introduction Gastric cancer remains a common cancer worldwide with an annual incidence of over 1,000,000 cases and an estimated of 783,000 deaths in 2018 [1]. More than 70% of these cases occur in developing countries, especially East Asia [2]. Despite decreased incidence in many developed nations, gastric cancer remains a significant public health problem in the USA. Moreover, the
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