When should I administer Phesgo (pertuzumab and trastuzumab) and when should I withhold it in patients with HER2-positive breast cancer?

From the Guidelines

Phesgo (pertuzumab and trastuzumab) should be administered to patients with HER2-positive breast cancer in the neoadjuvant setting (before surgery), adjuvant setting (after surgery), or for metastatic disease, as it has been shown to improve disease-free survival and overall survival in these patients 1. The standard dosing regimen begins with a loading dose of 1,200 mg pertuzumab/600 mg trastuzumab given subcutaneously over 8 minutes, followed by maintenance doses of 600 mg pertuzumab/600 mg trastuzumab every 3 weeks. Some key points to consider when deciding whether to administer Phesgo include:

• The patient's cardiac function, as Phesgo can increase the risk of cardiac dysfunction 1
• The patient's risk of recurrence, as those with high-risk disease may benefit from more aggressive treatment 1
• The patient's overall health and ability to tolerate treatment, as Phesgo can cause infusion-related reactions and other side effects 1

You should withhold Phesgo for patients experiencing:

• Significant cardiac dysfunction (left ventricular ejection fraction below 40% or a decrease of ≥10% from baseline to below 50%)
• Severe infusion-related reactions, or hypersensitivity reactions
• Interstitial lung disease or pneumonitis
• Pregnancy, unless the potential benefit justifies the risk to the fetus

Regular cardiac monitoring with echocardiogram or MUGA scan is essential before starting treatment and at regular intervals (typically every 3 months) during therapy. Phesgo works by targeting the HER2 receptor through complementary mechanisms - pertuzumab prevents receptor dimerization while trastuzumab blocks ligand-independent HER2 signaling and triggers antibody-dependent cellular cytotoxicity, providing dual HER2 blockade that enhances anti-tumor activity. It is also important to consider the patient's individual risk factors and overall health when making treatment decisions, and to consult with a healthcare professional to determine the best course of treatment.

From the FDA Drug Label

Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function. Evaluate cardiac function prior to and during treatment

The decision to administer or withhold Phesgo (pertuzumab and trastuzumab) in patients with HER2-positive breast cancer should be based on the following:

• Administer Phesgo as part of the treatment regimen for patients with HER2-positive metastatic breast cancer, locally advanced, inflammatory, or early stage breast cancer, as indicated in the prescribing information 2.
• Withhold Phesgo in patients with a confirmed clinically significant decrease in left ventricular function.
• Monitor cardiac function prior to and during treatment to assess the need for withholding Phesgo.
• Key considerations for administration or withholding include:
  • Cardiac function
  • Presence of hypersensitivity reactions or anaphylaxis
  • Other adverse reactions that may require discontinuation of treatment

From the Research

Administration of Phesgo (Pertuzumab and Trastuzumab)

• Phesgo, a fixed-dose combination of pertuzumab and trastuzumab, is administered subcutaneously in patients with HER2-positive breast cancer 3.
• The decision to administer Phesgo should be based on the patient's individual risk factors, such as node-positive or hormone receptor-negative disease 4, 5.

Indications for Administration

• Phesgo is indicated for patients with high-risk HER2-positive early breast cancer, including those with node-positive or hormone receptor-negative disease 4, 5.
• The addition of pertuzumab to trastuzumab-based adjuvant therapy has been shown to improve invasive disease-free survival (IDFS) in these patients 4, 5.

Withholding Phesgo

• Phesgo may not be necessary for patients with node-negative and small primary tumors, as pertuzumab treatment has been found to offer little benefit in these cases 6.
• The decision to withhold Phesgo should be based on a careful evaluation of the patient's individual risk factors and the potential benefits and risks of treatment 6, 4, 5.

Safety Considerations

• Phesgo has been associated with cardiac toxicity, although the risk is low 6, 5.
• The most common adverse effect associated with Phesgo is diarrhea, although most cases are not severe 6.
• Primary cardiac events remain less than 1% in both treatment groups 5.