Pertuzumab

• Pertuzumab is a monoclonal antibody primarily used for HER2-positive breast cancer.
• It works by inhibiting the dimerization of HER2 receptors, blocking cell growth and survival signals.
• Often used in combination with trastuzumab and chemotherapy in neoadjuvant, adjuvant, and metastatic settings.
• Common side effects include diarrhea, hair loss, and nausea, while serious risks can involve cardiac dysfunction and infusion reactions.
• Its use significantly improves progression-free and overall survival rates for eligible patients.

What is Pertuzumab used for?

Pertuzumab is a humanized monoclonal antibody that targets the HER2 (human epidermal growth factor receptor 2) protein. It is primarily used in the treatment of HER2-positive breast cancer, a specific subtype of breast cancer characterized by an overexpression of the HER2 protein on the surface of cancer cells. This overexpression leads to aggressive tumor growth and a poorer prognosis if left untreated.

The primary application for Pertuzumab is in the context of Pertuzumab treatment for HER2-positive breast cancer. It is typically administered in combination with trastuzumab (another HER2-targeted antibody) and chemotherapy. This combination therapy is approved for several stages of HER2-positive breast cancer:

• Neoadjuvant treatment: Administered before surgery to shrink tumors in early-stage, locally advanced, or inflammatory HER2-positive breast cancer.
• Adjuvant treatment: Given after surgery to reduce the risk of recurrence in early-stage HER2-positive breast cancer.
• Metastatic treatment: Used for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

According to the American Cancer Society, about 15-20% of breast cancers are HER2-positive, making targeted therapies like Pertuzumab crucial for this patient population. Its use has been shown to significantly improve progression-free survival and overall survival rates in clinical trials.

Pertuzumab Mechanism of Action

The mechanism of action of Pertuzumab involves its specific binding to the HER2 receptor. Unlike trastuzumab, which binds to a different domain of HER2, Pertuzumab binds to subdomain II of the extracellular domain of the HER2 protein. This binding site is critical because it prevents the HER2 receptor from pairing (dimerizing) with other HER family receptors, such as HER1, HER3, and HER4.

HER2 dimerization is a key step in activating intracellular signaling pathways that promote cell growth, survival, and proliferation in cancer cells. By blocking this dimerization, Pertuzumab effectively inhibits these pro-cancer signals. This inhibition leads to reduced cell growth, increased apoptosis (programmed cell death), and decreased angiogenesis (formation of new blood vessels that feed tumors). When used in combination with trastuzumab, the two antibodies provide a more comprehensive blockade of HER2 signaling, leading to enhanced anti-tumor activity compared to either agent alone.

Pertuzumab Side Effects and Warnings

While Pertuzumab is an effective treatment, it can cause a range of side effects, some of which can be serious. Patients receiving Pertuzumab should be closely monitored by their healthcare team.

Common side effects often include:

Serious warnings and potential adverse events associated with Pertuzumab include:

• Cardiac dysfunction: Pertuzumab, especially when used with trastuzumab and anthracycline-based chemotherapy, can lead to a decrease in left ventricular ejection fraction (LVEF), which may result in heart failure. Cardiac function should be assessed before and during treatment.
• Infusion-related reactions: Patients may experience acute reactions during or after infusion, including fever, chills, fatigue, headache, and allergic reactions. Severe reactions, though rare, can occur.
• Hypersensitivity reactions/anaphylaxis: Severe allergic reactions requiring immediate medical attention have been reported.
• Embryo-fetal toxicity: Pertuzumab can cause harm to a fetus when administered to a pregnant woman. Women of reproductive potential should use effective contraception during treatment and for 7 months after the last dose.

It is crucial for patients to report any new or worsening symptoms to their doctor promptly. The decision to use Pertuzumab is made after careful consideration of its benefits against potential risks, tailored to the individual patient’s condition and overall health.