Combination of | |
---|---|
Pertuzumab | HER2/neu receptor antagonist |
Trastuzumab | HER2/neu receptor antagonist |
Hyaluronidase | Endoglycosidase |
Clinical data | |
Trade names | Phesgo |
AHFS/ Drugs.com | Monograph |
License data | |
Pregnancy category |
|
Routes of administration | Subcutaneous |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
KEGG |
Pertuzumab/trastuzumab/hyaluronidase, sold under the brand name Phesgo, is a fixed-dose combination medication to treat adults with HER2-positive breast cancer that has spread to other parts of the body, and for treatment of adults with early HER2-positive breast cancer. [5] [6] It contains pertuzumab, trastuzumab, and hyaluronidase–zzxf. [5] It is injected under the skin via subcutaneous injection in the thigh. [5] In the European Union, Phesgo contains the active ingredients pertuzumab and trastuzumab along with the enzyme vorhyaluronidase alfa. [7]
The most common side effects include alopecia (hair loss), nausea, diarrhea, anemia (reduced number of red blood cells) and asthenia (lack of energy). [5] [8] [3] It can cause worsening of chemotherapy induced neutropenia (low level of white blood cells). [5] It may cause harm to a developing fetus or a newborn baby. [5]
HER2-positive breast cancer, which makes up approximately one-fifth of breast cancers, has too much of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. [5] Pertuzumab and trastuzumab bind to sites on HER2 and disrupt signaling to stop cancer cell growth. [5]
The fixed-dose combination is indicated for the treatment of early breast cancer (EBC):
and for the treatment of metastatic breast cancer (MBC):
The FDA label includes a boxed warning about the risk of potential heart failure, fetal harm, and lung toxicity. [5] [9]
The fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase was approved for medical use in the United States in June 2020. [5] [10]
The FDA's approval was based on the results of a non-inferiority study in participants with HER2-positive early breast cancer, which demonstrated the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase had comparable efficacy and safety as IV pertuzumab and IV trastuzumab, except for administration-related reactions, which were higher with the fixed-dose combination due to the subcutaneous route of administration. [5]
Efficacy was investigated in FeDeriCa (NCT03493854), an open-label, multicenter, randomized trial enrolling 500 participants with operable or locally advanced HER2-positive breast cancer. [8] Participants were randomized to receive neoadjuvant chemotherapy with concurrent administration of either the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase or intravenous pertuzumab and intravenous trastuzumab during the neoadjuvant and adjuvant therapies. [8]
The primary endpoint of FeDeriCa was non-inferiority of cycle 7 pertuzumab serum trough concentration comparing the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase to intravenous pertuzumab. [8] Secondary endpoints included cycle 7 trastuzumab serum trough concentration, pathological complete response (pCR), and safety. [8] The fixed-dose combination showed non-inferior pertuzumab and trastuzumab serum trough concentrations compared to intravenous pertuzumab and trastuzumab. [8] The pCR rate was 59.7% (95% CI: 53.3, 65.8) in the pertuzumab/trastuzumab/hyaluronidase arm and 59.5% (95% CI: 53.2, 65.6) in the intravenous pertuzumab and intravenous trastuzumab arm. [8] The safety profile of the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase is comparable to intravenous pertuzumab and trastuzumab, except for increased administration-related reactions. [8]
The FDA granted approval of Phesgo to Genentech Inc. [5]
On 12 November 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Phesgo, intended for the treatment of early and metastatic breast cancer. [11] The applicant for this medicinal product is Roche Registration GmbH. [11] Phesgo was approved for medical use in the European Union in December 2020. [3]
Combination of | |
---|---|
Pertuzumab | HER2/neu receptor antagonist |
Trastuzumab | HER2/neu receptor antagonist |
Hyaluronidase | Endoglycosidase |
Clinical data | |
Trade names | Phesgo |
AHFS/ Drugs.com | Monograph |
License data | |
Pregnancy category |
|
Routes of administration | Subcutaneous |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
KEGG |
Pertuzumab/trastuzumab/hyaluronidase, sold under the brand name Phesgo, is a fixed-dose combination medication to treat adults with HER2-positive breast cancer that has spread to other parts of the body, and for treatment of adults with early HER2-positive breast cancer. [5] [6] It contains pertuzumab, trastuzumab, and hyaluronidase–zzxf. [5] It is injected under the skin via subcutaneous injection in the thigh. [5] In the European Union, Phesgo contains the active ingredients pertuzumab and trastuzumab along with the enzyme vorhyaluronidase alfa. [7]
The most common side effects include alopecia (hair loss), nausea, diarrhea, anemia (reduced number of red blood cells) and asthenia (lack of energy). [5] [8] [3] It can cause worsening of chemotherapy induced neutropenia (low level of white blood cells). [5] It may cause harm to a developing fetus or a newborn baby. [5]
HER2-positive breast cancer, which makes up approximately one-fifth of breast cancers, has too much of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. [5] Pertuzumab and trastuzumab bind to sites on HER2 and disrupt signaling to stop cancer cell growth. [5]
The fixed-dose combination is indicated for the treatment of early breast cancer (EBC):
and for the treatment of metastatic breast cancer (MBC):
The FDA label includes a boxed warning about the risk of potential heart failure, fetal harm, and lung toxicity. [5] [9]
The fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase was approved for medical use in the United States in June 2020. [5] [10]
The FDA's approval was based on the results of a non-inferiority study in participants with HER2-positive early breast cancer, which demonstrated the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase had comparable efficacy and safety as IV pertuzumab and IV trastuzumab, except for administration-related reactions, which were higher with the fixed-dose combination due to the subcutaneous route of administration. [5]
Efficacy was investigated in FeDeriCa (NCT03493854), an open-label, multicenter, randomized trial enrolling 500 participants with operable or locally advanced HER2-positive breast cancer. [8] Participants were randomized to receive neoadjuvant chemotherapy with concurrent administration of either the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase or intravenous pertuzumab and intravenous trastuzumab during the neoadjuvant and adjuvant therapies. [8]
The primary endpoint of FeDeriCa was non-inferiority of cycle 7 pertuzumab serum trough concentration comparing the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase to intravenous pertuzumab. [8] Secondary endpoints included cycle 7 trastuzumab serum trough concentration, pathological complete response (pCR), and safety. [8] The fixed-dose combination showed non-inferior pertuzumab and trastuzumab serum trough concentrations compared to intravenous pertuzumab and trastuzumab. [8] The pCR rate was 59.7% (95% CI: 53.3, 65.8) in the pertuzumab/trastuzumab/hyaluronidase arm and 59.5% (95% CI: 53.2, 65.6) in the intravenous pertuzumab and intravenous trastuzumab arm. [8] The safety profile of the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase is comparable to intravenous pertuzumab and trastuzumab, except for increased administration-related reactions. [8]
The FDA granted approval of Phesgo to Genentech Inc. [5]
On 12 November 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Phesgo, intended for the treatment of early and metastatic breast cancer. [11] The applicant for this medicinal product is Roche Registration GmbH. [11] Phesgo was approved for medical use in the European Union in December 2020. [3]