Should I continue trastuzumab (Herceptin) maintenance in a patient with metastatic gastric cancer after 6 cycles of cisplatin, capecitabine, and trastuzumab?

Trastuzumab Maintenance Therapy in HER2-Positive Metastatic Gastric Cancer

Trastuzumab maintenance therapy should be continued until disease progression after completion of 6 cycles of cisplatin, capecitabine, and trastuzumab in patients with HER2-positive metastatic gastric cancer. 1

Evidence-Based Rationale

The FDA-approved trastuzumab label clearly indicates that in the pivotal ToGA trial, trastuzumab was administered until disease progression in patients with HER2-positive metastatic gastric cancer 1. This approach has become the standard of care based on the following evidence:

1. FDA Label Guidance: The trastuzumab drug label explicitly states that in the ToGA trial, trastuzumab was administered "until disease progression" 1.

2. NCCN Guidelines: The National Comprehensive Cancer Network (NCCN) guidelines for gastric cancer recommend continuation of targeted therapies like trastuzumab until evidence of disease progression or unacceptable toxicity 2.

3. Real-World Evidence: A Turkish Oncology Group retrospective study demonstrated that trastuzumab maintenance (median 13 cycles) after 6 cycles of chemotherapy plus trastuzumab showed efficacy with a median progression-free survival of 12.0 months and overall survival of 17.4 months with minimal toxicity 3.

Maintenance Therapy Options

After completing 6 cycles of cisplatin, capecitabine, and trastuzumab, the following maintenance approaches can be considered:

• Trastuzumab monotherapy: Continue trastuzumab alone until disease progression 1
• Trastuzumab plus capecitabine: This combination has shown efficacy in real-world studies 3

Clinical Considerations

Efficacy

• Continuation of trastuzumab after completion of chemotherapy is based on the design of the ToGA trial, which demonstrated improved overall survival (13.8 vs. 11.1 months) with trastuzumab plus chemotherapy compared to chemotherapy alone 1.
• The exploratory analysis of the ToGA trial showed that patients with the highest level of HER2 expression (IHC3+) had the greatest benefit from trastuzumab, with median OS of 17.9 months (vs. 12.3 months in the control arm) 1.

Safety

• Long-term trastuzumab maintenance has a manageable safety profile with cardiac toxicity being the main concern 3.
• Regular cardiac monitoring (every 3 months) is recommended during maintenance therapy.

Practical Approach

1. Complete 6 cycles of cisplatin, capecitabine, and trastuzumab
2. Assess disease status with imaging
3. If no progression:
   • Continue trastuzumab at 6 mg/kg IV every 3 weeks until disease progression
   • Consider adding capecitabine maintenance in patients with good performance status

Common Pitfalls to Avoid

1. Premature discontinuation: Stopping trastuzumab after 6 cycles may compromise survival outcomes as the drug is intended to be continued until progression.

2. Inadequate monitoring: Failing to monitor for cardiac toxicity during maintenance therapy.

3. Overlooking progression: Ensure regular imaging (every 2-3 months) to detect disease progression promptly.

4. Continuing chemotherapy indefinitely: While trastuzumab should be continued, the platinum agent (cisplatin) should be discontinued after 6 cycles to avoid cumulative toxicity.

In conclusion, based on the strongest evidence from the FDA label and clinical guidelines, trastuzumab maintenance therapy should be continued until disease progression in patients with HER2-positive metastatic gastric cancer who have completed 6 cycles of cisplatin, capecitabine, and trastuzumab.