Is starting a patient with HER2-positive breast cancer on neoadjuvant Adriamycin (Doxorubicin) and Cyclophosphamide (AC), then Phesgo (Pertuzumab and Trastuzumab) and Docetaxel a viable treatment option?

From the Guidelines

Starting a patient with HER2-positive breast cancer on neoadjuvant AC (Adriamycin/doxorubicin and cyclophosphamide) followed by Phesgo (pertuzumab and trastuzumab) with docetaxel is a viable and commonly used treatment approach, as supported by recent clinical guidelines and trials 1. This sequential regimen typically consists of 4 cycles of AC (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² every 2-3 weeks), followed by 4 cycles of docetaxel (75-100 mg/m²) with Phesgo (initial loading dose of 1200 mg pertuzumab/600 mg trastuzumab, then 600 mg pertuzumab/600 mg trastuzumab every 3 weeks).

Key Considerations

• The AC portion provides effective cytotoxic treatment, while the addition of dual HER2 blockade with pertuzumab and trastuzumab to taxane therapy significantly enhances pathologic complete response rates.
• Cardiac monitoring with echocardiograms or MUGA scans is essential before starting treatment and periodically throughout, as both anthracyclines and HER2-targeted agents can cause cardiotoxicity.
• Appropriate supportive care including antiemetics, growth factor support if needed, and close monitoring for side effects should be implemented.

Supporting Evidence

• The most recent guideline from 2021 recommends pertuzumab, trastuzumab, and docetaxel as the standard first-line treatment for HER2-positive metastatic breast cancer 1.
• Previous guidelines and studies have consistently supported the use of trastuzumab and taxane therapy in the treatment of HER2-positive breast cancer 1.

Clinical Implications

• This regimen has demonstrated improved pathologic complete response rates and is supported by major clinical trials in the neoadjuvant setting for HER2-positive breast cancer.
• Clinicians should consider the patient's overall health, cardiac function, and potential side effects when selecting a treatment regimen.

From the FDA Drug Label

Docetaxel Injection in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.

The use of neoadjuvant Adriamycin (Doxorubicin) and Cyclophosphamide (AC), then Phesgo (Pertuzumab and Trastuzumab) and Docetaxel is a viable treatment option for patients with HER2-positive breast cancer. This is because Docetaxel is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and it can be used in combination with other drugs like doxorubicin and cyclophosphamide for the adjuvant treatment of patients with operable node-positive breast cancer 2. However, it's essential to consider the patient's overall health, liver function, and potential side effects before starting this treatment regimen.

• Key considerations:
  • Monitor liver function and adjust the dose accordingly
  • Be aware of potential side effects like neutropenia, hypersensitivity reactions, and fluid retention
  • Use prophylactic G-CSF to mitigate the risk of hematological toxicities if necessary
  • Closely monitor patients, especially the elderly, for adverse reactions 2 2

From the Research

Treatment Overview

• The treatment of HER2-positive breast cancer often involves a combination of chemotherapy, targeted therapy, and sometimes hormone therapy.
• Neoadjuvant therapy, which is given before the main treatment (usually surgery), is commonly used to shrink tumors and make them easier to remove.

Neoadjuvant AC, then Phesgo and Docetaxel

• Starting a patient with HER2-positive breast cancer on neoadjuvant Adriamycin (Doxorubicin) and Cyclophosphamide (AC), then Phesgo (Pertuzumab and Trastuzumab) and Docetaxel is a viable treatment option 3.
• A study published in 2017 found that four cycles of docetaxel, cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2-positive primary breast cancer resulted in a pathological complete response (pCR) rate of 43.9% 3.
• Another study published in 2020 found that a docetaxel and cyclophosphamide regimen without anthracycline as neoadjuvant chemotherapy achieved a high clinical response rate in stage II to III ER+/HER2- breast cancer, but the pCR rate was not very high 4.
• The use of Phesgo, which is a combination of pertuzumab and trastuzumab, has been shown to improve outcomes in HER2-positive breast cancer patients when used in combination with docetaxel 5.

Efficacy and Safety

• The efficacy and safety of docetaxel and cyclophosphamide as neoadjuvant chemotherapy in HER2-negative primary breast cancer have been evaluated in several studies, with mixed results 4, 6.
• A study published in 2017 found that the pCR rate for patients with HER2-negative breast cancer treated with docetaxel and cyclophosphamide was 16.3% 6.
• The addition of trastuzumab to a non-anthracycline regimen, such as docetaxel and cyclophosphamide, has been shown to improve disease-free survival and overall survival in patients with HER2-amplified early stage breast cancer 5.

Conclusion Not Provided as per Request

• As per the request, no conclusion will be provided. However, it is essential to consider the patient's individual characteristics, such as hormone receptor status and tumor stage, when selecting a treatment regimen.
• Neoadjuvant treatment should be considered for all patients with HER2-positive or triple-negative breast cancer, as it can help identify new biomarkers that predict response or resistance to treatment 7.