On 29 June 2020, a novel fixed-dose combination of trastuzumab, pertuzumab, and hyaluronidase–zzxf (PHESGO, Genentech, Inc.) for subcutaneous injection to treat HERS-2 (human epidermal growth factor receptor 2) positive breast cancer was approved by US FDA (United States Food and Drug Administration).
It can be used in combination with chemotherapy as
- neoadjuvant treatment of patients suffering from HER2-positive, locally advanced, inflammatory, or early-stage breast cancer (either node-positive or greater than 2 cm in diameter) as part of a complete treatment regimen for the early stage of breast cancer
- adjuvant treatment of patients with HER2-positive early breast cancer at greater risk of recurrence
It can also be utilized in combination with docetaxel for the management of patients with HER2-positive metastatic breast cancer who have not been treated with prior anti-HER2 therapy or chemotherapy.
A randomized, open-label, multicentre clinical trial (FeDeriCa) was conducted to explore the efficacy of PHESGO. Overall, 500 operable or metastatic HER2-positive breast cancer patients were incorporated in the study. Subjects were randomized to either i.v (intravenous) administration of pertuzumab and trastuzumab during the neoadjuvant and adjuvant chemotherapy or neoadjuvant therapy with PHESGO.
Estimation of non-inferiority of cycle 7 pertuzumab serum trough concentration assessing PHESGO versus i.v pertuzumab was the primary outcome. Estimation of cycle 7 trastuzumab serum trough concentration, safety, and pCR (pathological complete response) were the secondary outcome measures.
In comparison with pertuzumab and trastuzumab, PHESGO illustrated non-inferior pertuzumab and trastuzumab serum trough concentrations. The values of the pCR rate in the PHESGO group and the i.v pertuzumab and trastuzumab group are shown in the following table:
PHESGO groupi.v pertuzumab and trastuzumab GROUPpCR rate59.70%59.50%
The safety profile of PHESGO was found to be similar to i.v pertuzumab and trastuzumab, except for elevated administration-related reactions. In >30% of patients receiving PHESGO, the most frequent adverse effects noted were nausea, diarrhea, asthenia, alopecia, and anemia.There are two phases of PHESGO dosing. PHESGO’s initial dose is subcutaneously given for approximately 8 minutes and contains trastuzumab 600 mg, pertuzumab 1,200 mg, and hyaluronidase 30,000 units. The second dose is given subcutaneously every 3 weeks for approximately 5 minutes and contains trastuzumab 600 mg, pertuzumab 600 mg, and hyaluronidase 20,000 units.All serious adverse effects suspected to be linked with the use of any device or medicine should be reported by healthcare professionals to FDA’s MedWatch Reporting System.
Source
https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-combination-pertuzumab-trastuzumab-and-hyaluronidase-zzxf-her2-positive-breast-cancer
Original title of the article FDA approves combination of pertuzumab, trastuzumab, and hyaluronidase-zzxf for HER2-positive breast cancer