FDA Approves Combination of Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf for HER2-Positive Breast Cancer

June 29, 2020

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On June 29, 2020, the Food and Drug Administration approved a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase–zzxf (PHESGO®, Genentech, Inc.) for subcutaneous injection for the following indications: 

  • Use in combination with chemotherapy as: 
    • neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer;
    • adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence.
  • Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Efficacy was investigated in FeDeriCa (NCT03493854), an open-label, multicenter, randomized trial enrolling 500 patients with operable or locally advanced HER2-positive breast cancer. Patients were randomized to receive neoadjuvant chemotherapy with concurrent administration of either PHESGO or intravenous pertuzumab and intravenous trastuzumab during the neoadjuvant and adjuvant therapies.

The primary endpoint of FeDeriCa was non-inferiority of cycle 7 pertuzumab serum trough concentration comparing PHESGO to intravenous pertuzumab. Secondary endpoints included cycle 7 trastuzumab serum trough concentration, pathological complete response (pCR), and safety. PHESGO showed non-inferior pertuzumab and trastuzumab serum trough concentrations compared to intravenous pertuzumab and trastuzumab. The pCR rate was 59.7% (95% CI: 53.3, 65.8) in the PHESGO arm and 59.5% (95% CI: 53.2, 65.6) in the intravenous pertuzumab and intravenous trastuzumab arm.  The safety profile of PHESGO is comparable to intravenous pertuzumab and trastuzumab, except for increased administration-related reactions.

The most common adverse reactions in >30% patients receiving PHESGO were alopecia, nausea, diarrhea, anemia, and asthenia.

The recommended initial dose of PHESGO is 1,200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase administered subcutaneously over approximately 8 minutes, followed every 3 weeks by a dose of 600 mg pertuzumab,

600 mg trastuzumab, and 20,000 units hyaluronidase administered subcutaneously over approximately 5 minutes.

View full prescribing information for PHESGO.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was approved 4 months prior to the FDA goal date.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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