What are the systemic treatment options for a patient with metastatic gastric cancer featuring a mixed histology of adenocarcinoma and neuroendocrine tumor (NET)?

From the Guidelines

Systemic treatment for metastatic gastric cancer with mixed adenocarcinoma and neuroendocrine tumor (NET) histology typically involves a combination approach targeting both components, with first-line therapy usually consisting of platinum-based chemotherapy regimens such as FOLFOX or CAPOX, combined with trastuzumab for HER2-positive tumors, as recommended by the most recent guidelines 1. The treatment approach should be individualized based on the patient's performance status, comorbidities, and molecular characteristics, including HER2, PD-L1, and MSI status. Some key points to consider in the treatment of metastatic gastric cancer with mixed histology include:

• The use of platinum-based chemotherapy regimens, such as FOLFOX or CAPOX, as first-line therapy 1
• The addition of trastuzumab to first-line chemotherapy for HER2-positive tumors 1
• The use of somatostatin analogs, such as octreotide LAR or lanreotide, for the NET component, particularly for functioning NETs causing carcinoid syndrome 1
• Second-line options, including irinotecan-based regimens, taxanes, or ramucirumab, with or without paclitaxel 1
• The consideration of immunotherapy with pembrolizumab for MSI-high/dMMR tumors 1
• Regular imaging every 2-3 months to assess treatment response and consideration for switching therapy if disease progression occurs 1. It is essential to note that the treatment selection should be guided by the predominant histology, tumor burden, molecular characteristics, and patient's performance status, and that multidisciplinary team management is crucial for the management of patients with gastric cancer 1.

From the Research

Systemic Treatment Options for Metastatic Gastric Cancer with Mixed Histology

• The treatment of metastatic gastric cancer with a mixed histology of adenocarcinoma and neuroendocrine tumor (NET) is challenging due to the heterogeneity of the disease 2.
• For adenocarcinoma components, fluoropyrimidines, platinum compounds, taxanes, and irinotecan are active drugs, with the combination of fluoropyrimidines and a platinum compound being the optimal first-line treatment 2.
• Trastuzumab and ramucirumab are targeted agents approved for the treatment of advanced gastric adenocarcinoma (AGC) in the first and second lines, respectively 2.
• For neuroendocrine tumor components, chemotherapy is considered the "state of the art" treatment, but there is no standard effective post-first-line treatment for relapsing high-grade gastroenteropancreatic neuroendocrine neoplasms 3.
• A case report suggests that a multimodality treatment approach, including chemotherapy, surgical resection, and radiotherapy, may be beneficial for gastric mixed adenoneuroendocrine carcinoma 4.
• The FOLFIRI regimen (fluorouracil, leucovorin, and irinotecan) has been shown to be an acceptable first-line treatment for advanced gastric adenocarcinoma, with better tolerance and similar efficacy compared to the ECX regimen (epirubicin, cisplatin, and capecitabine) 5.

Potential Treatment Approaches

• A combination of chemotherapy regimens targeting both adenocarcinoma and neuroendocrine tumor components, such as fluoropyrimidines and platinum compounds, may be considered 2, 3.
• Multimodality therapy, including chemotherapy, surgical resection, and radiotherapy, may be beneficial for patients with gastric mixed adenoneuroendocrine carcinoma 4.
• The use of targeted agents, such as trastuzumab and ramucirumab, may be explored in the treatment of metastatic gastric cancer with mixed histology, although their efficacy in this specific setting is unclear 2.