What is the role of Phesgo (pertuzumab and trastuzumab) in adjuvant treatment of HER2-positive early breast cancer?

Role of Phesgo in Adjuvant Treatment of HER2-Positive Early Breast Cancer

Phesgo (pertuzumab and trastuzumab) is indicated for adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence, particularly those with node-positive disease, where it significantly improves invasive disease-free survival when added to standard chemotherapy. 1

Patient Selection and Risk Stratification

The decision to use Phesgo in the adjuvant setting should be based on recurrence risk assessment:

High-Risk Patients (Recommended for Phesgo)

• Node-positive disease
• Tumors ≥2 cm in diameter
• Residual invasive disease after neoadjuvant therapy

Lower-Risk Patients (Consider Alternative Regimens)

• Node-negative disease with tumors <2 cm
• Complete pathological response (pCR) after neoadjuvant therapy

Evidence Supporting Adjuvant Phesgo Use

The APHINITY trial provides the strongest evidence for adjuvant pertuzumab-trastuzumab use. With 6 years of follow-up, the trial demonstrated:

• 24% relative reduction in recurrence risk (HRa 0.76; 95% CI 0.64-0.91) 2
• In node-positive disease: 6-year invasive disease-free survival (iDFS) was 87.9% with pertuzumab-trastuzumab vs 83.4% with trastuzumab alone (absolute difference 4.5%; HRa 0.72; 95% CI 0.59-0.87) 2
• No statistically significant benefit in node-negative disease (HRa 1.02; 95% CI 0.69-1.53) 2

Treatment Algorithm

1. Initial Risk Assessment

   • Evaluate nodal status, tumor size, hormone receptor status, and response to neoadjuvant therapy (if applicable)

2. Adjuvant Treatment Approach

   • For high-risk patients (node-positive): Phesgo plus chemotherapy for 1 year (18 cycles)
   • For low-risk patients (node-negative, tumor <2cm): Consider de-escalation with weekly paclitaxel for 12 weeks plus trastuzumab for 1 year 2

3. Post-Neoadjuvant Decision Making

   • If pCR achieved after neoadjuvant dual HER2 blockade: Continue pertuzumab-trastuzumab to complete 1 year of treatment 2
   • If residual disease present: Consider switching to T-DM1 for 14 cycles 2

Duration of Treatment

The standard duration of adjuvant Phesgo treatment is 1 year (18 cycles). Multiple trials have investigated shorter durations of trastuzumab (6 months), but results remain inconclusive, and 12 months remains the standard of care 2.

Safety Considerations

• Cardiac monitoring: Evaluate cardiac function prior to and during treatment due to risk of left ventricular dysfunction 1
• Diarrhea management: More common with pertuzumab-containing regimens (9.8% vs 3.7% grade 3 or higher), occurring primarily during chemotherapy 3
• Pregnancy prevention: Advise patients about embryo-fetal toxicity risks and need for effective contraception 1

Common Pitfalls to Avoid

1. Overtreatment of low-risk disease: Patients with node-negative, small tumors may not derive significant benefit from dual HER2 blockade

2. Undertreatment of high-risk disease: Node-positive patients should receive dual HER2 blockade to maximize outcomes

3. Failure to adjust therapy based on neoadjuvant response: Patients with residual disease after neoadjuvant therapy benefit from switching to T-DM1

4. Inadequate cardiac monitoring: Regular cardiac assessment is essential to detect and manage potential cardiac dysfunction

The evidence clearly supports using Phesgo in the adjuvant setting for patients with HER2-positive early breast cancer who have high-risk features, particularly node-positive disease, while considering more targeted approaches for those with lower-risk disease.