Pertuzumab/trastuzumab/hyaluronidase

Pertuzumab/trastuzumab/hyaluronidase
Combination of
PertuzumabHER2/neu receptor antagonist
TrastuzumabHER2/neu receptor antagonist
HyaluronidaseEndoglycosidase
Names
Trade namesPhesgo
Clinical data
Drug classMonoclonal antibodies[1]
Main usesHER2-positive breast cancer[2]
Side effectsHair loss, nausea, diarrhea, low red blood cells, weakness, joint pain[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • Not recommended
Routes of
use		Subcutaneous
External links
AHFS/Drugs.comMonograph
Legal
License data
Legal status

Pertuzumab/trastuzumab/hyaluronidase, sold under the brand name Phesgo, is a combination medication used to treat HER2-positive breast cancer.[2] It contains pertuzumab, trastuzumab, and hyaluronidase (vorhyaluronidase alfa).[2][3] It is injected under the skin.[2]

Common side effects include hair loss, nausea, diarrhea, low red blood cells, weakness, and joint pain.[1] Other side effect may include low white blood cells, infection, and heart failure.[1] Use during pregnancy may harm the baby.[4] Pertuzumab and trastuzumab are monoclonal antibodies which bind HER2 blocking signals for the cancer to grow.[1] Hyaluronidase is an enzyme that improve absorption of the other medication.[3]

The combination was approved for medical use in the United States and Europe in 2020.[4][1] In the United Kingdom the first dose costs the NHS about £6,000 with subsequent doses being £3,600 as of 2021.[5] In the United States this costs about 13,300 USD and 8,900 USD respectively.[6]

Medical uses

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

  • Use in combination with chemotherapy for:[7]
    • the neoadjuvant treatment of adults with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than two cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer;[7]
    • the adjuvant treatment of adults with HER2-positive early breast cancer at high risk of recurrence.[7]

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

  • Use in combination with docetaxel for the treatment of adults with HER2-positive metastatic breast cancer (MBC) who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.[7]

Dosage

It is given as an initial dose of 1200 mg pertuzumab / 600 mg trastuzumab.[1] Further doses are given every three weeks at a dose of 600 mg pertuzumab / 600 mg trastuzumab.[1]

Side effects

The FDA label includes a boxed warning about the risk of potential heart failure, fetal harm, and lung toxicity.[8][9]

History

The fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase was approved for medical use in the United States in June 2020.[8][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.[8]

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.[8]

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.[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.[1]

References

  1. 1 2 3 4 5 6 7 8 9 10 "Phesgo EPAR". European Medicines Agency (EMA). 13 October 2020. Archived from the original on 15 January 2021. Retrieved 14 January 2021.
  2. 1 2 3 4 "DailyMed - PHESGO- pertuzumab, trastuzumab, and hyaluronidase-zzxf injection, solution". dailymed.nlm.nih.gov. Archived from the original on 23 October 2021. Retrieved 27 October 2021.
  3. 1 2 "SUMMARY OF PRODUCT CHARACTERISTICS" (PDF). Archived (PDF) from the original on 20 October 2021. Retrieved 27 October 2021.
  4. 1 2 "Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Monograph for Professionals". Drugs.com. Archived from the original on 20 November 2020. Retrieved 27 October 2021.
  5. ↑ "Pertuzumab + trastuzumab". SPS - Specialist Pharmacy Service. 30 September 2018. Archived from the original on 23 January 2021. Retrieved 27 October 2021.
  6. ↑ "Phesgo Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 27 October 2021.
  7. 1 2 3 4 5 6 7 8 9 10 11 "FDA approves combination of pertuzumab, trastuzumab, and hyaluronidase". U.S. Food and Drug Administration (FDA). 29 June 2020. Archived from the original on 30 June 2020. Retrieved 29 June 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  8. 1 2 3 4 "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. Archived from the original on 29 June 2020. Retrieved 29 June 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  9. ↑ "Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection, for subcutaneous use" (PDF). Genentech, Inc. Archived (PDF) from the original on 30 June 2020. Retrieved 29 June 2020.
  10. ↑ "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. Archived from the original on 30 June 2020. Retrieved 29 June 2020 – via GlobeNewswire.
  11. 1 2 "Phesgo: Pending EC decision". European Medicines Agency (EMA). 11 November 2020. Archived from the original on 20 November 2020. Retrieved 13 November 2020.
Identifiers:
  • "Pertuzumab". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 27 March 2021. Retrieved 2 March 2021.
  • "Trastuzumab". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 4 March 2021. Retrieved 2 March 2021.
  • "Hyaluronidase". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 15 April 2021. Retrieved 2 March 2021.
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