Second-Line Treatment of Gastric Adenocarcinoma

EP: 1.Patient Profile: A 60-Year-Old Man with Stage IV Gastric Adenocarcinoma

EP: 2.Frontline Treatment Options for Gastric Adenocarcinoma

EP: 3.The Role of Immunotherapies in Upper GI Cancers

EP: 4.Managing Adverse Events from Immunotherapy in Upper Gastric Cancer

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EP: 5.Second-Line Treatment of Gastric Adenocarcinoma

EP: 6.Ongoing Research in Upper Gastric Cancer

EP: 7.The Future of Upper Gastric Cancer Treatment

Case: A 60-Year-Old Man with Stage IV Gastric Adenocarcinoma

Clinical Presentation:

• A 60-year-old man with abrupt 10-pound weight loss, dyspepsia, bloating after meals, and loss of appetite, and all symptoms worsening over the past three months.
• PMH and FHx: Overweight and HTN. Patients father deceased at age 50 due to gastric cancer.

Initial Clinical Workup and Diagnosis:

• EGD showed 2 cm protruding mass in the body of the stomach
  • No Ulcerations
  • Biopsy showed poorly differentiated adenocarcinoma
• Stage IV adenocarcinoma
• Molecular Testing: HER2/neu –; MMRp/MSS, PD-L1 CPS 5%
• CT of abdomen and chest reveal a gastric polypoid mass and thickening; No ascites; 2 lesions in the left lower lobe.
• Lung Biopsy: metastatic adenocarcinoma consistent with gastric primary
• PET/CT confirmed metastatic disease

Current Treatments:

• Patient was initiated on FOLFOX +nivolumab

This is a video synopsis/summary of a Case-Based Peer Perspectives series featuring David Zhen, MD.

After progression on first-line therapy with chemotherapy and immunotherapy for metastatic gastric cancer, standard cytotoxic regimens remain the primary treatment options. These include taxanes, such as paclitaxel or docetaxel, often combined with VEGF inhibitors like ramucirumab. Irinotecan-based treatments, either alone or in combination with 5-fluorouracil (5-FU) and leucovorin to form FOLFIRI, are also viable options. Additionally, trifluridine/tipiracil (TAS-102) demonstrated a modest survival benefit compared with placebo.

Zhen notes that while paclitaxel with ramucirumab is often preferred as a second-line treatment, there is no data demonstrating superiority among the available options. The choice of treatment may depend on patient factors, such as the presence of neuropathy from prior platinum exposure. In HER2-positive gastric cancer, trastuzumab can be added to chemo-immunotherapy in the first-line setting due to its synergistic effect with immunotherapy through antibody-dependent cellular cytotoxicity.

In the refractory setting, novel agents like trastuzumab deruxtecan are now approved for advanced gastric cancer after progression on trastuzumab. While continuing immunotherapy beyond progression is not recommended, ongoing clinical trials are evaluating the combination of immunotherapy with other agents to overcome resistance.

Video synopsis is AI-generated and reviewed by Targeted Oncology™ editorial staff.