On June 29, the U.S. Food and Drug Administration (FDA) approved a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf (Phesgo) for subcutaneous injection in the following indications:
- Use in combination with chemotherapy as:
- Neoadjuvant treatment for 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 who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
“Currently, most patients with HER2-positive breast cancer receive trastuzumab and pertuzumab at infusion centers. With a new administration route, [this triplet] offers an outpatient option for patients to receive trastuzumab and pertuzumab,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
Richard Pazdur, MD
FeDeriCa Trial
Efficacy was investigated in FeDeriCa, an open-label, multicenter, randomized trial that enrolled 500 patients with operable or locally advanced HER2-positive breast cancer. Patients were randomly assigned to receive neoadjuvant chemotherapy with concurrent administration of either the triplet combination or intravenous pertuzumab and intravenous trastuzumab during the neoadjuvant and adjuvant therapies.
The primary endpoint of FeDeriCa was noninferiority of cycle 7 pertuzumab serum trough concentration comparing pertuzumab/trastuzumab/hyaluronidase-zzxf to intravenous pertuzumab. Secondary endpoints included cycle 7 trastuzumab serum trough concentration, pathologic complete response, and safety.
Pertuzumab/trastuzumab/hyaluronidase-zzxf showed noninferior pertuzumab and trastuzumab serum trough concentrations compared to intravenous pertuzumab and trastuzumab. The pathologic complete response rate was 59.7% (95% confidence interval [CI] = 53.3%–65.8%) in the pertuzumab/trastuzumab/hyaluronidase-zzxf arm and 59.5% (95% CI = 53.2%–65.6%) in the intravenous pertuzumab and intravenous trastuzumab arm.
The safety profile of pertuzumab/trastuzumab/hyaluronidase-zzxf is comparable to intravenous pertuzumab and trastuzumab, except for increased administration-related reactions. The most common adverse reactions in > 30% patients receiving the triplet combination were alopecia, nausea, diarrhea, anemia, and asthenia.
The recommended initial dose of pertuzumab/trastuzumab/hyaluronidase-zzxf is 1,200 mg of pertuzumab, 600 mg of trastuzumab, and 30,000 units of hyaluronidase administered subcutaneously over approximately 8 minutes, followed every 3 weeks by a dose of 600 mg of pertuzumab, 600 mg of trastuzumab, and 20,000 units of hyaluronidase administered subcutaneously over approximately 5 minutes.
