What is the recommended first-line systemic therapy for a patient with metastatic gastric adenocarcinoma to the liver and lungs?

First-Line Systemic Therapy for Metastatic Gastric Adenocarcinoma to Liver and Lungs

For a patient with metastatic gastric adenocarcinoma to the liver and lungs, the recommended first-line systemic therapy is a fluoropyrimidine (5-FU or capecitabine) plus cisplatin combination, with trastuzumab added if the tumor is HER2-positive. 1

Initial Assessment

1. HER2 testing is mandatory before initiating therapy as it determines treatment selection
2. Performance status evaluation to determine if patient can tolerate doublet vs. triplet regimens
3. Assessment of comorbidities that might contraindicate specific agents

Treatment Algorithm Based on HER2 Status

HER2-Positive Disease

• First choice: Trastuzumab + fluoropyrimidine (5-FU or capecitabine) + cisplatin (Category 1/Evidence 1A) 1
• Alternative: Trastuzumab + fluoropyrimidine + oxaliplatin (Evidence 2B) 1
• Important: Avoid combining trastuzumab with anthracyclines due to cardiac toxicity risk 1

HER2-Negative Disease

• First choice: Fluoropyrimidine (5-FU or capecitabine) + cisplatin (Category 1/Evidence 1A) 1
• Alternative options:
  • Fluoropyrimidine + oxaliplatin (Evidence 2B) 1
  • Paclitaxel + fluoropyrimidine (Evidence 2B) 1
  • FOLFIRI (fluorouracil, leucovorin, irinotecan) 1

Special Considerations

For Patients with Good Performance Status (ECOG 0-1)

• Consider triplet regimens in select patients with good performance status and high tumor burden:
  • DCF (docetaxel, cisplatin, 5-FU) or modified DCF 1, 2
  • FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) 3

The FLOT regimen has shown promising results with a median overall survival of 13.5 months and objective response rate of 64.8% in metastatic gastric cancer 3, but two-drug regimens are generally preferred due to lower toxicity.

For Patients with Poor Performance Status (ECOG 2)

• Single-agent therapy with fluoropyrimidine or taxane 1

Practical Considerations

• Infusional 5-FU is preferred over bolus administration 1
• Capecitabine can be substituted for infusional 5-FU in most regimens 1
• Oxaliplatin can replace cisplatin if there are concerns about renal function or fluid status 1
• Dose modifications may be necessary based on toxicities and patient tolerance

Common Pitfalls to Avoid

1. Failing to test for HER2 status before initiating therapy
2. Using triplet regimens in patients with poor performance status - reserve for medically fit patients with good PS and access to frequent toxicity monitoring
3. Combining trastuzumab with anthracyclines due to increased cardiac toxicity
4. Overlooking supportive care - aggressive management of symptoms like nausea, vomiting, and nutritional support is essential
5. Delaying assessment of response - early evaluation is important to identify non-responders who may benefit from switching to second-line therapy

The choice between doublet and triplet regimens should be based on the patient's performance status, comorbidities, and the urgency of response needed. While triplet regimens may achieve higher response rates, they are associated with increased toxicity and should be reserved for medically fit patients who can tolerate the additional side effects.