Ongoing Research in Upper Gastric Cancer

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

EP: 5.Second-Line Treatment of Gastric Adenocarcinoma

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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.

The treatment landscape for HER2-positive gastric cancer is rapidly evolving. In the first-line setting, the KEYNOTE-811 trial investigated the addition of pembrolizumab to chemotherapy plus trastuzumab, the current standard of care. Despite an initial accelerated approval based on impressive objective response rates, the final analysis revealed a survival benefit only in patients with a PD-L1 combined positive score of 1% or above, leading to a recent FDA indication change.

In the second-line setting, the antibody-drug conjugate (ADC) trastuzumab deruxtecan has shown impressive results compared with standard chemotherapy, overcoming HER2 resistance through the bystander effect, where the drug conjugate leaks into HER2-negative cells.

Ongoing trials are examining the role of immunotherapy in earlier-stage settings, with data on pathological complete response rates, but longer-term data on disease-free survival are needed.

The SPOTLIGHT and GLOW trials demonstrated the benefit of combining the monoclonal antibody zolbetuximab, which targets Claudin-18.2, with FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) in the first-line setting for Claudin 18.2-expressing cancers. An FDA approval is expected soon, leading to the development of novel therapies like ADCs and chimeric antigen receptor T-cell therapies for progressive disease after targeted agents.

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