What is the next step for a patient who has received four cycles of Phesgo (pertuzumab, trastuzumab, and hyaluronidase) and docetaxel in the neoadjuvant setting?

Next Steps After Neoadjuvant Phesgo and Docetaxel in Breast Cancer

After completing four cycles of Phesgo (pertuzumab, trastuzumab, and hyaluronidase) and docetaxel in the neoadjuvant setting, the patient should continue Phesgo to complete a total of one year of therapy (up to 18 cycles) while proceeding with surgery and appropriate adjuvant therapy.

Treatment Algorithm After Neoadjuvant Phesgo and Docetaxel

Immediate Next Steps

1. Proceed to surgery (definitive breast surgery)
2. Continue Phesgo therapy after surgery to complete a full year of treatment
3. Consider additional chemotherapy based on pathological response

Complete Treatment Pathway

Surgical Phase

• Definitive breast surgery should be performed after completion of the neoadjuvant chemotherapy
• Timing: Typically 3-4 weeks after completion of neoadjuvant therapy to allow for recovery

Adjuvant Systemic Therapy

• Continue Phesgo (pertuzumab/trastuzumab/hyaluronidase):

  • Continue every 3 weeks to complete a total of one year of therapy (up to 18 cycles) 1
  • This includes the cycles already received in the neoadjuvant setting
  • Cardiac monitoring should be performed at baseline, 3,6, and 9 months 2

• Additional Chemotherapy Options (if pathological complete response not achieved):

  • FEC (5-fluorouracil, epirubicin, cyclophosphamide) for 3-4 cycles 1, 3
  • This regimen is commonly used following neoadjuvant taxane-based therapy

Radiation Therapy

• Should be administered after completion of chemotherapy
• Typically begins 3-4 weeks after surgery or after completion of adjuvant chemotherapy

Endocrine Therapy

• For hormone receptor-positive disease:
  • Start after completion of chemotherapy
  • Continue for 5-10 years depending on risk factors

Evidence-Based Rationale

The FDA-approved regimen for Phesgo in the neoadjuvant setting is based on the NeoSphere trial, which demonstrated that pertuzumab plus trastuzumab and docetaxel significantly improved pathological complete response rates compared to trastuzumab plus docetaxel alone (39.3% vs. 21.5%) 1, 3. Following surgery, patients in this trial received FEC chemotherapy and continued trastuzumab to complete one year of therapy.

The drug label for pertuzumab and trastuzumab clearly states: "Following surgery, patients should continue to receive PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk to complete 1 year of treatment (up to 18 cycles)" 1.

Important Considerations

Cardiac Monitoring

• LVEF assessment is required before initiating Phesgo and at regular intervals (baseline, 3,6, and 9 months) during treatment 2
• Monitor for signs and symptoms of cardiac dysfunction

Pathological Response Assessment

• The pathological complete response (pCR) rate will guide further treatment decisions
• Patients with residual disease may benefit from additional adjuvant chemotherapy

Common Pitfalls to Avoid

1. Premature discontinuation of Phesgo: Completing the full year of therapy is critical for optimal outcomes
2. Inadequate cardiac monitoring: Regular cardiac assessment is essential to detect early signs of cardiotoxicity
3. Delaying surgery: Surgery should proceed within 3-6 weeks after completing neoadjuvant therapy
4. Overlooking hormone therapy: For hormone receptor-positive disease, endocrine therapy is an essential component of the treatment plan

By following this algorithm, the patient will receive the complete standard of care treatment for HER2-positive breast cancer in the neoadjuvant setting, which has been shown to improve disease-free survival and overall survival.