Should I start treatment with AC followed by Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase) plus Docetaxel for a patient with early HER2-positive breast cancer?

From the Guidelines

For a patient with early HER2-positive breast cancer, starting treatment with AC (doxorubicin and cyclophosphamide) followed by Phesgo (pertuzumab, trastuzumab, and hyaluronidase) plus docetaxel is a highly recommended approach, as it has been shown to significantly improve disease-free survival and overall survival compared to chemotherapy with trastuzumab alone 1. This treatment strategy is supported by recent clinical trials, including the APHINITY study, which demonstrated the efficacy of dual HER2 blockade with pertuzumab and trastuzumab in combination with chemotherapy for patients with HER2-positive early breast cancer 1. The standard regimen typically consists of 4 cycles of AC given every 2-3 weeks, followed by 4 cycles of Phesgo plus docetaxel every 3 weeks, with Phesgo then continued to complete a full year of HER2-targeted therapy. Some key points to consider when implementing this treatment plan include:

• Baseline cardiac function should be assessed with an echocardiogram or MUGA scan, as both anthracyclines and HER2-targeted therapies can affect heart function 1.
• Regular cardiac monitoring should continue throughout treatment to minimize the risk of cardiotoxicity 1.
• Phesgo offers the advantage of subcutaneous administration, reducing infusion time compared to intravenous trastuzumab and pertuzumab. The APHINITY study results, as outlined in Table 1 of the 2021 Cancer Treatment Reviews article 1, provide strong evidence for the effectiveness of this treatment approach in improving invasive disease-free survival (IDFS) and overall survival (OS) for patients with HER2-positive early breast cancer. Overall, the combination of AC followed by Phesgo plus docetaxel is a well-supported treatment strategy for patients with early HER2-positive breast cancer, offering improved outcomes and a more convenient administration option with Phesgo.

From the FDA Drug Label

Use in combination with trastuzumab and chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. PERJETA should be administered every 3 weeks for 3 to 6 cycles as part of one of the following treatment regimens for early breast cancer Four preoperative cycles of dose-dense doxorubicin and cyclophosphamide (ddAC) alone followed by 4 preoperative cycles of PERJETA in combination with paclitaxel and trastuzumab or trastuzumab hyaluronidase-oysk PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk should start on Day 1 of the first taxane-containing cycle

The recommended treatment regimen for a patient with early HER2-positive breast cancer is to start with AC (dose-dense doxorubicin and cyclophosphamide) followed by Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase) plus Docetaxel 2. Key points to consider:

• PERJETA should be administered every 3 weeks for 3 to 6 cycles as part of a treatment regimen for early breast cancer.
• Taxane should be administered after PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk.
• The initial dose of PERJETA is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks by a dose of 420 mg administered as an intravenous infusion over 30 to 60 minutes.
• Phesgo can be given in any order with PERJETA and trastuzumab or trastuzumab hyaluronidase-oysk 2.

From the Research

Treatment Approach for Early HER2-Positive Breast Cancer

• The treatment approach for early HER2-positive breast cancer often involves a combination of chemotherapy, targeted therapy, and sometimes hormone therapy, depending on the hormone receptor status of the tumor.
• Studies have shown that the use of pertuzumab and trastuzumab in combination with chemotherapy can improve outcomes in patients with HER2-positive breast cancer 3, 4.

Neoadjuvant Therapy with AC and Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase) plus Docetaxel

• Neoadjuvant therapy with four cycles of adriamycin and cyclophosphamide (AC) followed by four cycles of docetaxel, in combination with trastuzumab, has been shown to be effective in patients with high-risk, early-stage, HER2-positive breast cancer 5.
• The addition of pertuzumab to trastuzumab and docetaxel has been shown to improve pathological complete response rates in patients with HER2-positive breast cancer 3, 6.
• Phesgo, a fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase, has been approved for use in combination with chemotherapy for the treatment of HER2-positive breast cancer.

Efficacy and Safety of the Proposed Treatment Regimen

• The efficacy and safety of the proposed treatment regimen, starting with AC and later Phesgo plus docetaxel, would depend on various factors, including the patient's overall health, tumor characteristics, and prior treatments.
• Studies have shown that the combination of pertuzumab, trastuzumab, and docetaxel can be effective in achieving pathological complete response in patients with HER2-positive breast cancer, with acceptable safety profiles 3, 4, 6.

Considerations for Treatment Decision-Making

• When deciding on a treatment regimen for a patient with early HER2-positive breast cancer, it is essential to consider the patient's individual characteristics, tumor biology, and prior treatments.
• The treatment regimen should be tailored to the patient's specific needs, and the potential benefits and risks of each treatment option should be carefully weighed 7, 3, 4, 6.