Pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (PhesgoTM) was approved by the U.S. Food and Drug Administration (FDA) in June 2020 for patients with advanced HER2-positive breast cancer. The drug components are the same as those in the FDA-approved IV version, and study results showed comparable safety and efficacy to the IV counterparts. The new administration route allows eligible patients to bypass infusion centers or even receive the therapy at home.

Class

Pertuzumab and trastuzumab are HER2/neu receptor antagonists and hyaluronidase is an endoglycosidase.

Indications

Patients with HER2-positive breast cancer (as confirmed by an FDA-approved companion diagnostic test) may receive the therapy as:

  • Neoadjuvant treatment of locally advanced, inflammatory, or early-stage cancer
  • Adjuvant treatment for early-stage cancer with a high risk of recurrence
  • In combination with docetaxel for metastatic cancer with no prior therapy for metastatic disease

Administration and Dosage

Give as one subcutaneous injection, alternating sites between the left and right thigh. The initial dose is 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered subcutaneously over eight minutes. Maintenance doses every three weeks are 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously over five minutes.

Adverse Events

The medication has a black box warning for cardiomyopathy, embryo-fetal toxicity, and pulmonary toxicity. For neoadjuvant and adjuvant treatment, the most common adverse reactions were alopecia, anemia, asthenia, diarrhea, and nausea. For metastatic breast cancer, the most common adverse reactions were alopecia, diarrhea, fatigue, neutropenia, nausea, peripheral neuropathy, and rash.

Nursing Considerations 

Evaluate cardiac function with a multigated acquisition (MUGA) scan before starting and when indicated during therapy. Left ventricular ejection fraction (LVEF) should be at least 55% for early-stage breast cancer and at least 50% for metastatic disease; dose modifications may be needed for dysfunction. If possible, patients should avoid anthracycline-based therapy for up to seven months after stopping treatment. If patients received previous anthracycline-based therapy, LVEF must be at least 50% before starting pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection.

Monitor patients for signs and symptoms of infection from neutropenia. Also monitor for hypersensitivity reactions during and 30 minutes after the initial dose and for 15 minutes after maintenance doses. Permanently discontinue therapy after anaphylaxis or severe hypersensitivity reactions. Verify patients’ pregnancy status before administration.

Patient Education

Instruct patients to report any of the following symptoms immediately: new or worsening shortness of breath, cough, swelling in the ankles or legs, facial swelling, palpitations, weight gain of more than five pounds in 24 hours, dizziness, loss of consciousness, nausea, chills, fever, vomiting, diarrhea, urticaria, angioedema, or chest pain. Educate pregnant patients and those of reproductive ability that exposure to the treatment during pregnancy or within seven months prior to conception can result in fetal harm. Patients should use effective contraception during treatment and for seven months following their last dose. 

Gero-Oncology Considerations 

The drug’s clinical trials did not include enough patients aged 65 years or older to determine whether they respond differently from younger patients. In the IV pertuzumab and trastuzumab trials, older patients had increased risk of cardiac dysfunction, decreased appetite, anemia, weight loss, asthenia, dysgeusia, peripheral neuropathy, and hypomagnesemia.

Safe Handling

Pertuzumab, trastuzumab, and hyaluronidase-zzxf is associated with embryo-fetal toxicity.

Patient Assistance

Genentech Access Solutions is available online.