Advances in the Treatment of Gastric Cancer

David H. Ilson

Disclosures

Curr Opin Gastroenterol. 2020;36(6):525-529. 

In This Article

Abstract and Introduction

Abstract

Purpose of Review: To provide an up-to-date review on the management of cancers of the stomach and esophagogastric junction (EGJ).

Recent Findings: Microsatellite instable (MSI) high status in gastric cancer may portend a relatively good prognosis and indicate that adjuvant chemotherapy is of no added benefit to primary surgical management. In the preoperative treatment of HER2 (ErbB2)-positive EGJ adenocarcinoma with chemoradiotherapy, the addition of trastuzumab, a recombinant humanized mAb directed against the extracellular domain of Her2, failed to improve outcome over conventional chemoradiotherapy alone. Escalating the dose of radiation in combined chemoradiotherapy regimens did not improve survival over conventional dose radiotherapy in the nonoperative management of EGJ cancer. The use of proton vs. conventional external beam radiation therapy, although potentially less toxic, did not improve therapy outcome with preoperative or definitive chemoradiotherapy in EGJ cancer. In metastatic HER2-positive gastric cancer, after disease progression on trastuzumab, continuation of trastuzumab did not improve progression free or overall survival compared with second-line chemotherapy alone. However, in the setting or prior trastuzumab therapy in metastatic HER2-positive gastric cancer, the new agent trastuzumab deruxtecan achieved significant rates of response, progression free and overall survival compared with standard chemotherapy. After initial chemotherapy for metastatic esophagogastric cancer, maintenance therapy with the anti PDL-1 agent avelumab was no better than chemotherapy alone.

Summary: MSI high gastric cancer has a better prognosis and may not require adjuvant chemotherapy. Trastuzumab, added to preoperative chemoradiotherapy in HER2-positive esophageal adenocarcinoma, does not improve outcome. Dose escalation of radiotherapy in the nonoperative management of EGJ cancer does not improve local control or survival, and proton therapy may not achieve superior outcomes compared with external beam radiotherapy. In metastatic HER2-positive gastric cancer, continuing trastuzumab into second-line chemotherapy does not add benefit; however, the novel agent trastuzumab deruxtecan has substantial activity after prior trastuzumab-based therapy.

Introduction

Gastric cancer is the fifth most common cancer and the third most common cause of cancer-related death globally.[1] Adjuvant chemotherapy, given as pre or postoperative therapy, improves survival compared with surgery alone. Current adjuvant chemotherapy standards include FLOT (infusional 5-FU, leucovorin, oxaliplatin, and docetaxel) given pre and postoperatively, S-1/oxaliplatin postoperatively for 6 months (node-positive disease), S-1/docetaxel postoperatively for 1 year (node-positive disease), or S-1 alone for 1 year (node-negative disease). Postoperative radiation therapy does not improve outcome after gastrectomy in both Western and Asian trials and should not be routinely administered. For esophagogastric junction (EGJ) cancers, however, a combination of preoperative chemotherapy and radiation followed by surgery remains the standard of care. Chemotherapy for metastatic gastric cancer traditionally combines a fluorinated pyrimidine with a platinum agent; if patients are HER2-positive, trastuzumab, a recombinant humanized mAb directed against the extracellular domain of Her2, is included in first-line chemotherapy. Second-line chemotherapy combines paclitaxel with the vascular endothelial growth factor receptor 2 antagonist, ramucirumab. Immune checkpoint inhibitors are approved for treatment of patients with chemotherapy refractory metastatic gastric cancer who test PDL-1 positive; these agents may be used as earlier line therapy in microsatellite instable (MSI) high cancers.

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