Pertuzumab/trastuzumab/hyaluronidase

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Pertuzumab/trastuzumab/hyaluronidase
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
  • Not recommended
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. [4] [5] It contains pertuzumab, trastuzumab, and hyaluronidase–zzxf. [4] It is injected under the skin via subcutaneous injection in the thigh. [4] In the European Union, Phesgo contains the active ingredients pertuzumab and trastuzumab along with the enzyme vorhyaluronidase alfa. [6]

Contents

The most common side effects include alopecia (hair loss), nausea, diarrhea, anemia (reduced number of red blood cells) and asthenia (lack of energy). [4] [7] [2] It can cause worsening of chemotherapy induced neutropenia (low level of white blood cells). [4] It may cause harm to a developing fetus or a newborn baby. [4]

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. [4] Pertuzumab and trastuzumab bind to sites on HER2 and disrupt signaling to stop cancer cell growth. [4]

Medical uses

The fixed-dose combination is indicated for the treatment of early breast cancer (EBC):

and for the treatment of metastatic breast cancer (MBC):

Adverse effects

The FDA label includes a boxed warning about the risk of potential heart failure, fetal harm, and lung toxicity. [4] [8]

History

The fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase was approved for medical use in the United States in June 2020. [4] [9]

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. [4]

Efficacy was investigated in FeDeriCa (NCT03493854), an open-label, multicenter, randomized trial enrolling 500 participants with operable or locally advanced HER2-positive breast cancer. [7] 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. [7]

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. [7] Secondary endpoints included cycle 7 trastuzumab serum trough concentration, pathological complete response (pCR), and safety. [7] The fixed-dose combination showed non-inferior pertuzumab and trastuzumab serum trough concentrations compared to intravenous pertuzumab and trastuzumab. [7] 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. [7] 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. [7]

The FDA granted approval of Phesgo to Genentech Inc. [4]

Society and culture

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. [10] The applicant for this medicinal product is Roche Registration GmbH. [10] Phesgo was approved for medical use in the European Union in December 2020. [2]

Related Research Articles

Genentech, Inc. is an American biotechnology corporation headquartered in South San Francisco, California. It became an independent subsidiary of Roche in 2009. Genentech Research and Early Development operates as an independent center within Roche. Historically, the company is regarded as the world's first biotechnology company.

<span class="mw-page-title-main">Trastuzumab</span> Medication

Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin.

<span class="mw-page-title-main">Hyaluronidase</span> Class of enzymes

Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid. Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyaluronidases are two classes of eukaryotic endoglycosidase hydrolases and a prokaryotic lyase-type of glycosidase.

Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).

<span class="mw-page-title-main">Lapatinib</span> Cancer medication

Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).

<span class="mw-page-title-main">Pertuzumab</span> Pharmaceutical drug

Pertuzumab, sold under the brand name Perjeta, is a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it also used in the same combination as a neoadjuvant in early HER2-positive breast cancer.

<span class="mw-page-title-main">Neratinib</span> Chemical compound

Neratinib (INN), sold under the brand name Nerlynx, is a tyrosine kinase inhibitor anti-cancer medication used for the treatment of breast cancer.

<span class="mw-page-title-main">Olaparib</span> Chemical compound (cancer therapy drug)

Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers.

<span class="mw-page-title-main">Trastuzumab emtansine</span> Pharmaceutical drug

Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death. Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells. The conjugate is abbreviated T-DM1.

Margetuximab, sold under the brand name Margenza, is a chimeric IgG monoclonal antibody medication against HER2 used for the treatment of cancer.

<span class="mw-page-title-main">Pembrolizumab</span> Pharmaceutical drug used in cancer treatment

Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.

<span class="mw-page-title-main">Copanlisib</span> Chemical compound

Copanlisib, sold under the brand name Aliqopa, is a medication used for the treatment of adults experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies.

<span class="mw-page-title-main">Atezolizumab</span> Monoclonal anti-PD-L1 antibody

Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).

<span class="mw-page-title-main">Sacituzumab govitecan</span> Antibody-drug conjugate

Sacituzumab govitecan, sold under the brand name Trodelvy, is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate used for the treatment of metastatic triple-negative breast cancer and metastatic urothelial cancer.

<span class="mw-page-title-main">Alpelisib</span> Chemical compound

Alpelisib, sold under the brand name Piqray among others, is a medication used to treat certain types of breast cancer. It is used together with fulvestrant. It is taken by mouth. It is marketed by Novartis.

<span class="mw-page-title-main">Elacestrant</span> Chemical compound

Elacestrant, sold under the brand name Orserdu, is an anticancer medication which is used in the treatment of breast cancer. It is taken by mouth.

<span class="mw-page-title-main">Tucatinib</span> Chemical compound

Tucatinib, sold under the brand name Tukysa, is an anticancer medication used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of HER2. It was developed by Array BioPharma and licensed to Cascadian Therapeutics.

<span class="mw-page-title-main">Halozyme</span> Biotechnology company

Halozyme Therapeutics is an American biotechnology company. It develops oncology therapies designed to target the tumor microenvironment.

<span class="mw-page-title-main">Trastuzumab deruxtecan</span> Medication

Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan. It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell.

Trastuzumab/hyaluronidase, sold under the brand name Herceptin SC among others, is a fixed-dose combination medication for the treatment of HER2-overexpressing breast cancer in adults. It is a combination of trastuzumab and hyaluronidase.

References

  1. ↑ "Phesgo- pertuzumab, trastuzumab, and hyaluronidase-zzxf injection, solution". DailyMed. Retrieved 22 October 2021.
  2. 1 2 3 "Phesgo EPAR". European Medicines Agency (EMA). 13 October 2020. Retrieved 14 January 2021.
  3. ↑ "Phesgo Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA Approves Breast Cancer Treatment That Can Be Administered At Home By Health Care Professional". U.S. Food and Drug Administration (Press release). 29 June 2020. Retrieved 29 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  5. ↑ Skidmore-Roth L (2021). "Pertuzumab/trastuzumab/hyaluronidase-zzxf (Rx)". Mosby's Drug Guide for Nursing Students with 2022 Update - E-Book (14th ed.). Elsevier Health Sciences. p. 1213. ISBN   978-0-323-87656-8.
  6. ↑ "Phesgo 600 mg/600 mg solution for injection" (PDF). Roche Pharma AG. European Medicines Agency. 21 December 2020.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA approves combination of pertuzumab, trastuzumab, and hyaluronidase". U.S. Food and Drug Administration (FDA). 29 June 2020. Retrieved 29 June 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  8. ↑ "Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection, for subcutaneous use" (PDF). Genentech, Inc. Retrieved 29 June 2020.
  9. ↑ "FDA approves Roche's Phesgo (fixed-dose combination of Perjeta and Herceptin for subcutaneous injection) for HER2-positive breast cancer". F. Hoffmann-La Roche Ltd (Press release). 29 June 2020. Retrieved 29 June 2020– via GlobeNewswire.
  10. 1 2 "Phesgo: Pending EC decision". European Medicines Agency (EMA). 11 November 2020. Retrieved 13 November 2020.

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