Pertuzumab (Perjeta) - Uses, Dose, Side effects

Pertuzumab is a monoclonal antibody used in cancer treatment. It is sold under the brand name Perjeta. Pertuzumab is primarily used in combination with other drugs to treat certain types of breast cancer.

The primary indication for pertuzumab is in the treatment of HER2-positive breast cancer. HER2 (human epidermal growth factor receptor 2) is a protein that promotes the growth of cancer cells. Pertuzumab works by binding to the HER2 receptor, preventing it from activating cell growth signals and inhibiting the growth of cancer cells.

Pertuzumab is typically used in combination with trastuzumab (Herceptin) and chemotherapy drugs, such as docetaxel. This combination therapy is often referred to as dual HER2 blockade. By targeting HER2 through different mechanisms, pertuzumab and trastuzumab work synergistically to enhance the effectiveness of treatment.


Indications of Pertuzumab (Perjeta):

  • Metastatic breast cancer:

    • It is used for the treatment of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer concurrently with trastuzumab and docetaxel in patients who have not received prior anti-HER2 therapy or chemotherapy to treat metastatic disease.
  • Early breast cancer:

    • It is used for adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence concurrently with trastuzumab and chemotherapy.
  • Early breast cancer:

    • It is indicated for neoadjuvant treatment of locally advanced, inflammatory, or an early stage HER2-positive, breast cancer (>2 cm in diameter or node-positive) in combination with trastuzumab and chemotherapy as part of a complete treatment regimen for early breast cancer.

Pertuzumab (Perjeta) dose in adults:

Note:

  • When using a combination of pertuzumab, trastuzumab, and taxane drugs for breast cancer treatment, it is important to follow a specific order. Pertuzumab and trastuzumab can be given in any order, but the taxane should always be administered after pertuzumab and trastuzumab.
  • If the treatment regimen includes anthracycline therapy, pertuzumab (and trastuzumab) should be given after completing the anthracycline treatment.
  • After each pertuzumab infusion, it is necessary to monitor patients for 30 to 60 minutes before administering subsequent infusions of trastuzumab or docetaxel. This monitoring period helps ensure the patient's safety and allows healthcare professionals to observe any immediate adverse reactions.

 

Pertuzumab (Perjeta) dose in the treatment of metastatic HER2+ breast cancer:

  • Pertuzumab is given through an intravenous (IV) infusion.
  • The initial dose is 840 mg, which is administered over a period of 60 minutes.
  • After the initial dose, a maintenance dose of 420 mg is given over 30 to 60 minutes.
  • This maintenance dose is repeated every 3 weeks until either the disease progresses or the patient experiences unacceptable side effects.
  • It's important to note that pertuzumab is usually administered in combination with trastuzumab and docetaxel, as these drugs work together to treat breast cancer.

Pertuzumab (Perjeta) dose in the adjuvant treatment of early HER2+ breast cancer:

  • In the adjuvant treatment of early HER2+ breast cancer, pertuzumab is administered intravenously (IV).
  • The initial dose is 840 mg, given over a period of 60 minutes.
  • Following the initial dose, a maintenance dose of 420 mg is administered over 30 to 60 minutes.
  • This maintenance dose is given every 3 weeks for a total of 1 year or up to 18 cycles, whichever occurs first.
  • Pertuzumab is used as part of a combination regimen that includes trastuzumab and standard anthracycline- and/or taxane-based therapy.
  • Both pertuzumab and trastuzumab should be initiated on day 1 of the first taxane-containing cycle.

Pertuzumab (Perjeta) dose in the neoadjuvant treatment of early HER2+ breast cancer:

  • In neoadjuvant treatment of early HER2+ breast cancer, pertuzumab is given intravenously (IV).
  • The initial dose is 840 mg, administered over 60 minutes.
  • This is followed by a maintenance dose of 420 mg, given over 30 to 60 minutes.
  • The maintenance dose is repeated every 3 weeks for 3 to 6 cycles, depending on the specific treatment regimen chosen.

The treatment plan may consist of one of the following regimens:

Treatment Regimen

Before Surgery

After Surgery

Regimen 1: Pertuzumab, Trastuzumab, Docetaxel, followed by FEC

Four cycles of pertuzumab, trastuzumab, and docetaxel

Three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC)

Regimen 2: FEC, followed by Pertuzumab, Trastuzumab, Docetaxel

Three or four cycles of FEC

Three or four cycles of pertuzumab, trastuzumab, and docetaxel

Regimen 3: Pertuzumab, Trastuzumab, Docetaxel, Carboplatin

Six cycles of pertuzumab, trastuzumab, docetaxel, and carboplatin

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Regimen 4: Dose-dense Doxorubicin, Cyclophosphamide, followed by Pertuzumab, Trastuzumab, Paclitaxel

Four cycles of dose-dense doxorubicin and cyclophosphamide

Four cycles of pertuzumab, trastuzumab, and paclitaxel

Please note that for Regimen 3, no specific information provided about after surgery. Additionally, the information provided here is based on the sources mentioned (Gianni 2012, Schneeweiss 2013, and Swain 2018)

  • After surgery, trastuzumab should be continued to complete a total of 1 year of treatment.

Missed Doses or Delays:

If a pertuzumab dose is missed or delayed, the appropriate action depends on the duration of the interval:

  • If less than 6 weeks have passed since the last dose, administer the 420 mg maintenance dose. It is not necessary to wait until the next scheduled dose.
  • If 6 weeks or more have passed since the last dose, the treatment is restarted with the 840 mg initial dose (over 60 minutes), followed by the maintenance dose of 420 mg (over 30 to 60 minutes) every 3 weeks.

Use in Children:

The safety and efficacy of the drug in children is not established.


Pregnancy Risk Category: D

  • Pertuzumab can be harmful to unborn babies and cause birth defects.
  • It is important to inform patients about these risks and the importance of using effective contraception.
  • Pertuzumab, similar to other drugs in its class, may lead to a condition called oligohydramnios, which can result in underdeveloped lungs, skeletal problems, and even death in newborns.
  • If pertuzumab exposure occurs during pregnancy or within 7 months before conception, monitor for signs of oligohydramnios and conduct appropriate testing for the baby's well-being.
  • Limited information is available about accidental exposure to pertuzumab in combination with trastuzumab during pregnancy (Yildirim 2018).
  • The European Society for Medical Oncology (ESMO) guidelines recommend delaying treatment with HER2-targeted agents until after delivery in pregnant patients with HER2-positive disease (Peccatori 2013).
  • Before starting treatment, assess the pregnancy status of females who could become pregnant.
  • Use effective contraception during pertuzumab therapy and continue it for 7 months after the last dose, when pertuzumab is used together with trastuzumab.
  • If there is a suspicion of pregnancy during treatment, patients should immediately inform their healthcare provider.

Use of Pertuzumab while breastfeeding

  • It is unclear whether pertuzumab can be found in breast milk.
  • Breastfeeding while receiving pertuzumab should be carefully considered by weighing the potential risk to the infant and the benefits of breastfeeding for the infant against the benefits of treatment for the mother.
  • The prolonged half-life of pertuzumab and the 7-month washout period for trastuzumab should also be taken into account when making decisions about breastfeeding after treatment is finished.

Pertuzumab (Perjeta) Dose adjustment in renal disease:

  • For patients with a creatinine clearance (CrCl) of 30 mL/minute or higher, no adjustment in the dosage of pertuzumab is necessary.
  • For patients with a CrCl less than 30 mL/minute, the manufacturer's labeling does not provide specific dosage adjustment recommendations as it has not been studied in this populatio

Pertuzumab (Perjeta) Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer's labeling.


Common Side Effects of Pertuzumab (Perjeta):

  • Central Nervous System:
    • Fatigue
    • Headache
    • Decreased Left Ventricular Ejection Fraction
    • Insomnia
    • Dizziness
  • Dermatologic:
    • Alopecia
    • Skin Rash
    • Pruritus
    • Palmar-Plantar Erythrodysesthesia
    • Xeroderma
  • Gastrointestinal:
    • Diarrhea
    • Nausea
    • Vomiting
    • Decreased Appetite
    • Mucositis
    • Constipation
    • Stomatitis
    • Dysgeusia
  • Hematologic & Oncologic:
    • Neutropenia
    • Anemia
    • Leukopenia
    • Febrile Neutropenia
  • Hypersensitivity:
    • Hypersensitivity
  • Neuromuscular & Skeletal:
    • Asthenia
    • Myalgia
    • Arthralgia
  • Respiratory:
    • Upper Respiratory Tract Infection
    • Epistaxis
  • Miscellaneous:
    • Fever
    • Infusion Reactions

Rare Side Effects Of Pertuzumab:

  • Cardiovascular:
    • Left Ventricular Dysfunction
    • Peripheral Edema
  • Central Nervous System:
    • Peripheral Sensory Neuropathy
    • Peripheral Neuropathy
  • Dermatologic:
    • Nail Disease
    • Paronychia
  • Gastrointestinal:
    • Dyspepsia
  • Hematologic & Oncologic:
    • Thrombocytopenia
  • Hepatic:
    • Increased Serum Alanine Aminotransferase
  • Ophthalmic:
    • Increased Lacrimation
  • Respiratory:
    • Dyspnea
    • Nasopharyngitis
    • Oropharyngeal Pain
    • Cough

Contraindications to Pertuzumab:

Pertuzumab is contraindicated (should not be used) in the following situations:

  • Known hypersensitivity: Individuals with a known hypersensitivity or allergic reaction to pertuzumab or any of its components should not receive pertuzumab.

Warnings and precautions

Cardiotoxicity: [US Boxed Warning]

  • Pertuzumab has a boxed warning about the risk of cardiotoxicity, which may lead to decreased left ventricular ejection fraction (LVEF) and heart failure (HF).
  • Patients should have their cardiac function assessed at baseline and regularly during treatment.
  • If a confirmed clinically significant decline in left ventricular function is observed, pertuzumab should be discontinued.
  • Patients with pre-existing conditions that could impair LV function, such as uncontrolled hypertension, recent myocardial infarction, serious arrhythmia requiring treatment, or a history of exposure to high doses of anthracyclines, are excluded from clinical studies.
  • LVEF should be monitored at baseline and approximately every 12 weeks during treatment, and pertuzumab and trastuzumab should be withheld if LVEF declines below the threshold for metastatic or early breast cancer.
  • Repeat LVEF assessment in approximately 3 weeks and consider discontinuing pertuzumab if LVEF has not improved or has declined further.

Adverse events in the GI:

  • Gastrointestinal (GI) adverse events, specifically diarrhea, were reported more frequently in patients receiving pertuzumab in combination with trastuzumab and docetaxel compared to patients receiving only trastuzumab and docetaxel.
  • The occurrence of diarrhea was higher during the first cycle of pertuzumab treatment and was generally mild to moderate (grade 1 or 2).
  • In most cases, diarrhea could be managed with the use of loperamide and rarely led to a need for treatment delay.
  • It is important for healthcare providers to monitor and manage diarrhea effectively during pertuzumab treatment.

Hypersensitivity

  • Pertuzumab can cause severe hypersensitivity reactions, including anaphylaxis, which can be fatal. Angioedema has also been reported.
  • The risk of hypersensitivity reactions was slightly higher in patients receiving pertuzumab in combination with trastuzumab and docetaxel compared to those receiving placebo.
  • Patients should be closely monitored for signs of hypersensitivity reactions during treatment.
  • Healthcare providers should have medications and equipment ready to treat hypersensitivity reactions in case they occur during infusion.

Infusion reaction

  • Infusion reactions have been associated with pertuzumab, including fatal events, and monitoring is necessary.
  • Infusion reactions can occur during or on the day of infusion, and may include hypersensitivity, anaphylactic reaction, acute infusion reaction, or cytokine release during the infusion or on the same day as the infusion.
  • Other common infusion reactions may include fever, chills, fatigue, headache, weakness, myalgia, abnormal taste, and/or vomiting.
  • Grade 3 or 4 infusion reactions are rare but possible. It is recommended to monitor patients for at least 1 hour after the first infusion and for 30 minutes after subsequent infusions.
  • For significant infusion reactions, the infusion rate should be interrupted or slowed, and appropriate supportive management should be administered. For severe infusion reactions, permanent discontinuation may be necessary.

Monitoring parameters:

HER2 Expression:

  • Pertuzumab is used for HER2-positive breast cancer.
  • HER2 expression should be assessed to determine the appropriateness of pertuzumab treatment.

Pregnancy Test:

  • In females of reproductive potential, a pregnancy test should be conducted before starting pertuzumab treatment to ensure that the patient is not pregnant.

Assessment of Left Ventricular Ejection Fraction (LVEF):

  • LVEF should be evaluated at baseline before starting pertuzumab treatment.
  • Subsequent LVEF assessments should be performed approximately every 12 weeks during treatment, and more frequently if there are any declines or concerns about cardiac function.

Monitoring for Infusion Reaction:

  • During pertuzumab infusion and for a certain duration afterward, patients should be monitored for any signs of infusion reactions such as hypersensitivity, anaphylactic reactions, acute infusion reactions, or cytokine release.
  • Monitoring for 60 minutes following the initial pertuzumab infusion and for 30 minutes after subsequent infusions is recommended.

Diarrhea Monitoring:

  • Diarrhea is a potential side effect of pertuzumab treatment.
  • Patients should be monitored for the occurrence of diarrhea, especially during the first cycle of pertuzumab treatment.
  • Most cases are mild to moderate and can be managed with loperamide.

Hypersensitivity Monitoring:

  • Hypersensitivity reactions, including severe reactions, have been associated with pertuzumab.
  • Patients should be monitored for any signs of hypersensitivity reactions during treatment.

How to administer Pertuzumab (Perjeta)?

Intravenous (IV) Infusion:

  • Pertuzumab is administered through IV infusion only. It should not be given as an IV push or rapid bolus.

Infusion Duration:

  • The initial dose of pertuzumab, which is 840 mg, should be infused over a period of 60 minutes.
  • The maintenance dose of 420 mg should be infused over 30 to 60 minutes.

Mixing with Other Medications:

  • Pertuzumab should not be mixed with any other medications or substances.

Combination Regimens:

  • When pertuzumab is used in combination with trastuzumab and a taxane, pertuzumab and trastuzumab can be administered in any order.
  • However, the taxane should be given after pertuzumab and trastuzumab.

Timing with Anthracycline Therapy:

  • In patients receiving anthracycline-based regimens, pertuzumab (and trastuzumab) should be administered after completion of the anthracycline therapy.

Observation Period:

  • After each pertuzumab infusion, patients should be observed for 30 to 60 minutes before subsequent infusions of trastuzumab or docetaxel.
  • This observation period helps monitor for any immediate adverse reactions or hypersensitivity.

Hypersensitivity Monitoring:

  • Hypersensitivity reactions should be monitored for 60 minutes following the initial pertuzumab infusion and for 30 minutes following subsequent infusions.

Mechanism of action of Pertuzumab (Perjeta):

  • Pertuzumab is a type of medication known as a recombinant humanized monoclonal antibody.
  • It specifically targets a protein called human epidermal growth factor receptor 2 (HER2) in the body.
  • HER2 plays a role in promoting the growth of certain cancer cells, particularly in breast cancer.
  • The main mechanism of action of pertuzumab is to inhibit the dimerization (pairing) of HER2 proteins and block downstream signaling pathways.
  • By doing so, pertuzumab effectively stops the growth of cancer cells and promotes programmed cell death, known as apoptosis.
  • What makes pertuzumab unique is that it binds to a different region of the HER2 protein compared to another medication called trastuzumab.
  • When pertuzumab is used in combination with trastuzumab, it leads to a more comprehensive and effective inhibition of HER2 signaling.
  • This combined approach, targeting different regions of HER2, helps to maximize the therapeutic benefits in treating HER2-positive breast cancer.

Distrubition:

  • The volume of distribution (V) of pertuzumab is approximately 5.12 liters. This parameter reflects the apparent space in the body where pertuzumab is distributed.

Half-life elimination:

  • The elimination half-life of pertuzumab is approximately 18 days during the terminal phase. The half-life represents the time it takes for the concentration of pertuzumab in the body to decrease by half during the elimination process.

International Brands of Pertuzumab:

  • Perjeta

Pertuzumab Brands in Pakistan:

No Brands Available in Pakistan.

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