What chemotherapy regimen is recommended for recurrent serous carcinoma of the endometrium with Her2/neu (Human Epidermal growth factor Receptor 2/neu) positivity?

Treatment for Recurrent Serous Carcinoma Endometrium with HER2/neu Positivity

For recurrent serous carcinoma of the endometrium with HER2/neu positivity, the preferred chemotherapy regimen is carboplatin/paclitaxel/trastuzumab. 1

First-line Treatment Options

Preferred Regimen

• Carboplatin/paclitaxel/trastuzumab is the recommended triplet therapy for HER2-positive uterine serous carcinoma as a first-line option for recurrent disease 1
• This regimen has shown significant improvement in progression-free survival (PFS) compared to carboplatin/paclitaxel alone (12.6 months vs 8.0 months; p=0.005) 2, 3
• For patients with recurrent disease specifically, PFS improved from 6.0 months to 9.2 months with the addition of trastuzumab (p=0.003) 3
• Overall survival was also improved with the triplet regimen (29.6 months vs 24.4 months) 2

Dosing

• Carboplatin (AUC 5) + paclitaxel (175 mg/m²) + trastuzumab (6 mg/kg) 1
• Trastuzumab should be continued as maintenance therapy until progression or unacceptable toxicity 2, 3

Alternative Options if Trastuzumab Contraindicated

• Carboplatin/paclitaxel is the standard backbone chemotherapy regimen if trastuzumab cannot be used 1
  • Response rates range from 40% to 62% with this doublet regimen 1
  • Overall survival is approximately 13 to 29 months 1
• Carboplatin/docetaxel can be considered for patients in whom paclitaxel is contraindicated 1

Second-line Options

If disease progresses after first-line therapy, options include:

• Single-agent therapy with:
  • Cisplatin 1
  • Carboplatin 1
  • Doxorubicin or liposomal doxorubicin 1
  • Paclitaxel or albumin-bound paclitaxel 1
  • Topotecan 1
  • Bevacizumab (for patients who have progressed on previous cytotoxic chemotherapy) 1
• For carcinosarcoma histology specifically:
  • Ifosfamide 1
  • Ifosfamide/paclitaxel 1
  • Ifosfamide/cisplatin 1

Biomarker-Directed Options

• For patients with dMMR/MSI-H tumors who have received prior systemic therapy:
  • Dostarlimab 1
  • Nivolumab 1
  • Avelumab 1
• For NTRK gene fusion-positive tumors:
  • Larotrectinib or entrectinib (category 2B) 1

Important Considerations

HER2 Testing

• Proper HER2 testing is crucial for patient selection 4, 5
• Approximately 25-30% of endometrial serous carcinomas overexpress HER2 4
• Endometrial carcinoma-specific HER2 scoring criteria should be used rather than breast cancer criteria 5

Toxicity Considerations

• The addition of trastuzumab to carboplatin/paclitaxel does not significantly increase overall toxicity 1, 3
• Main toxicities with carboplatin/paclitaxel regimens are hematologic and neurologic (sensory neuropathy) 6
• Monitor for cardiac toxicity with trastuzumab

Common Pitfalls

• Failure to test for HER2 status in serous carcinoma of the endometrium 4
• Using inappropriate HER2 testing criteria (breast cancer criteria instead of endometrial-specific) 5
• Not continuing trastuzumab as maintenance therapy after completion of chemotherapy 2, 3
• Not considering alternative targeted therapies based on biomarker status (dMMR/MSI-H, NTRK fusions) 1

Treatment Algorithm

1. Confirm HER2/neu positivity with appropriate testing
2. For first-line therapy of recurrent disease:
   • If HER2-positive: Carboplatin/paclitaxel/trastuzumab followed by trastuzumab maintenance
   • If HER2-negative or trastuzumab contraindicated: Carboplatin/paclitaxel
3. Upon progression, consider single-agent therapy options based on prior treatment exposure and patient factors
4. For patients with specific biomarkers (dMMR/MSI-H, NTRK fusions), consider appropriate targeted therapies