Role of Phesgo (Pertuzumab and Trastuzumab) in Adjuvant Therapy for HER2-Positive Early Breast Cancer
Phesgo (pertuzumab-trastuzumab) should be used as adjuvant therapy in patients with HER2-positive early breast cancer who have node-positive disease, as it significantly reduces the risk of recurrence compared to trastuzumab alone. 1
Patient Selection for Phesgo in Adjuvant Setting
Phesgo combines two HER2-targeted agents (pertuzumab and trastuzumab) in a fixed-dose subcutaneous injection. The decision to use Phesgo in the adjuvant setting should be based on the following risk stratification:
High-Risk Patients (Recommended for Phesgo)
- Node-positive disease (strongest indication)
- Tumors ≥2 cm in diameter
- Both HR-positive and HR-negative subtypes benefit
Low-Risk Patients (Consider Trastuzumab Alone)
- Node-negative disease (pT1 pN0)
- Tumors <2 cm in diameter
Evidence Supporting Adjuvant Phesgo
The APHINITY trial provides the strongest evidence for dual HER2 blockade in the adjuvant setting. With longer follow-up (8 years), the node-positive subgroup maintained a clear invasive disease-free survival (iDFS) benefit with pertuzumab-trastuzumab, showing an 8-year iDFS of 86% versus 81% with trastuzumab alone (hazard ratio 0.72,95% CI 0.60-0.87) 1.
Key findings:
- No significant benefit was observed in node-negative patients
- Both hormone receptor-positive and negative cohorts derived benefit
- The absolute improvement in iDFS at 8 years was 4.5% 1
- No significant overall survival benefit has been demonstrated yet, but data remain immature 1
Treatment Duration and Administration
- Standard duration: 1 year (18 cycles given every 3 weeks) 1
- Attempts to shorten treatment duration to 6 months have shown inconclusive results 1
- Phesgo can be administered as a subcutaneous injection, which is more convenient than IV administration
Treatment Algorithm
Initial Assessment:
- Confirm HER2 positivity (IHC 3+ or IHC 2+ with positive ISH) 2
- Determine nodal status and tumor size
- Assess hormone receptor status
Treatment Pathway Decision:
- For clinical stage II-III disease: Consider neoadjuvant therapy first
- For smaller tumors (stage I): Consider upfront surgery
Adjuvant Therapy After Surgery:
Post-Neoadjuvant Pathway:
Chemotherapy Backbone Options
Phesgo can be combined with different chemotherapy regimens:
- Anthracycline-taxane based combinations (standard approach)
- Non-anthracycline regimens (e.g., carboplatin-taxane) for patients with cardiac risk factors 1
- For low-risk disease (pT1 pN0): Weekly paclitaxel for 12 weeks with trastuzumab for 1 year 1
Monitoring and Safety Considerations
- Cardiac monitoring is essential due to potential cardiotoxicity 2
- Evaluate left ventricular ejection fraction (LVEF) prior to and during treatment
- Discontinue treatment for clinically significant decrease in left ventricular function
- Diarrhea is more common with pertuzumab-containing regimens (9.8% vs 3.7% grade ≥3) 3
Clinical Pearls and Pitfalls
- Pitfall: Using dual HER2 blockade in all patients regardless of risk. This provides minimal benefit in node-negative patients while increasing toxicity and costs.
- Pitfall: Failing to consider the post-neoadjuvant setting. Patients with residual disease after neoadjuvant therapy benefit more from switching to T-DM1 rather than continuing Phesgo.
- Pearl: The benefit of dual HER2 blockade appears to increase over time, with greater separation of survival curves at later follow-up points.
- Pearl: The subcutaneous formulation (Phesgo) offers significant convenience advantages over IV administration while maintaining efficacy.
In conclusion, Phesgo represents an important advancement in adjuvant therapy for HER2-positive early breast cancer, with clear benefits in node-positive disease. Treatment decisions should be based on careful risk assessment, with dual HER2 blockade reserved primarily for patients with higher-risk features.