What is the adjuvant of choice for Human Epidermal growth factor Receptor 2 (HER2) positive breast cancer with and without Polymerase Chain Reaction (PCR)?

From the Guidelines

For HER2-positive breast cancer, the adjuvant therapy of choice is completion of anti-HER2 therapy with trastuzumab to complete a full year of treatment, often combined with pertuzumab, for patients who achieve pathologic complete response (pCR), and T-DM1 (trastuzumab emtansine) for 14 cycles for patients without pCR (residual disease). This recommendation is based on the most recent guidelines, including the NCCN Clinical Practice Guidelines in Oncology [ 1 ], which suggest that patients with residual disease after neoadjuvant therapy have a higher risk of recurrence and benefit from the more potent targeted therapy provided by T-DM1. Some key points to consider in the management of HER2-positive breast cancer include:

• The use of trastuzumab and pertuzumab in the neoadjuvant setting for high-risk patients [ 1 ]
• The importance of completing a full year of anti-HER2 therapy with trastuzumab, often combined with pertuzumab, for patients who achieve pCR [ 1 ]
• The use of T-DM1 for 14 cycles for patients without pCR (residual disease) [ 1 ]
• The consideration of extended adjuvant neratinib following adjuvant trastuzumab-containing therapy for patients with HR-positive, HER2-positive disease with a perceived high risk of recurrence [ 1 ]
• The addition of hormone therapy for hormone receptor-positive disease in both scenarios [ 1 ] Regular cardiac monitoring is essential during anti-HER2 therapy due to potential cardiotoxicity [ 1 ]. It is also important to note that the treatment recommendations should be consistent with local and international guidelines, and that further studies will guide optimization of treatment for patients with HER2-positive breast cancer according to the risk of disease recurrence [ 1 ].

From the FDA Drug Label

1 INDICATIONS AND USAGE 1.1 Adjuvant Breast Cancer Ogivri is indicated in adults for adjuvant treatment of HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature [see Clinical Studies (14. 1)]) breast cancer as part of a treatment regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel as part of a treatment regimen with docetaxel and carboplatin as a single agent following multi-modality anthracycline based therapy.

The adjuvant of choice for HER2 positive breast cancer is trastuzumab as part of a treatment regimen, as indicated in the drug label for Ogivri 2.

• Trastuzumab is indicated for adjuvant treatment of HER2 overexpressing node positive or node negative breast cancer.
• The treatment regimen consists of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel, or docetaxel and carboplatin. There is no information regarding PCR in the provided drug labels.

From the Research

Adjuvant Therapy for HER2-Positive Breast Cancer

• The adjuvant treatment of choice for HER2-positive breast cancer is a combination of chemotherapy and targeted therapy, specifically trastuzumab and pertuzumab 3, 4, 5, 6, 7.
• Trastuzumab has been shown to significantly improve disease-free and overall survival in patients with HER2-positive breast cancer when given in combination with or in sequence to adjuvant chemotherapy 4, 5.
• The addition of pertuzumab to trastuzumab and chemotherapy has been shown to further improve outcomes, including overall survival and pathologic complete response rate 3, 6, 7.
• Dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab is likely the best treatment option in terms of overall survival gain 7.

Treatment Options with and without PCR

• For patients with HER2-positive breast cancer, the treatment options with and without PCR (pathologic complete response) are similar, with a focus on combination therapy including trastuzumab and pertuzumab 3, 6, 7.
• The rates of pathologic complete response with neoadjuvant doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab and pertuzumab are high, ranging from 53% to 72% 6.
• The use of dual anti-HER2 blockade with trastuzumab plus pertuzumab has been shown to be effective in achieving pathologic complete response, even in patients with locally advanced disease 6.

Chemotherapy Regimens

• Various chemotherapy regimens have been studied in combination with trastuzumab and pertuzumab, including doxorubicin and cyclophosphamide followed by paclitaxel 6.
• The choice of chemotherapy regimen may depend on individual patient factors, such as tumor size and hormone receptor status 4, 5.
• The use of dose-dense chemotherapy regimens, such as doxorubicin and cyclophosphamide followed by paclitaxel, has been shown to be effective in achieving pathologic complete response 6.