Usage
Pertuzumab is prescribed for the treatment of HER2-positive breast cancer. This includes:
- Early-stage breast cancer: Used in combination with trastuzumab and chemotherapy in the neoadjuvant (before surgery) and adjuvant (after surgery) settings for patients at high risk of recurrence.
- Metastatic breast cancer: Used in combination with trastuzumab and docetaxel for patients who haven’t received prior anti-HER2 therapy or chemotherapy for metastatic disease.
Pharmacological Classification: Monoclonal antibody; antineoplastic agent.
Mechanism of Action: Pertuzumab targets HER2, a protein overexpressed in certain breast cancers. It binds to a specific region of HER2, preventing it from pairing with other HER receptors (dimerization), thus blocking cancer cell growth signals. It also promotes antibody-dependent cell-mediated cytotoxicity (ADCC).
Alternate Names
International Nonproprietary Name (INN): Pertuzumab
Brand Name: Perjeta, Phesgo (in combination with trastuzumab and hyaluronidase-zzfx)
How It Works
Pharmacodynamics: Pertuzumab primarily works by inhibiting HER2 signaling pathways, leading to cell growth arrest and apoptosis (programmed cell death). This effect is enhanced when combined with trastuzumab, which binds to a different part of HER2. Pertuzumab also facilitates ADCC, whereby immune cells destroy the cancer cells.
Pharmacokinetics:
- Absorption: Administered intravenously; steady-state concentration reached after the first maintenance dose. Subcutaneous administration is available with Phesgo (combined with trastuzumab and hyaluronidase-zzfx for increased absorption).
- Metabolism: Primarily cleared by catabolism (protein breakdown), similar to other antibodies. Not metabolized by CYP enzymes.
- Elimination: Half-life approximately 18 days (can vary depending on disease state).
Mode of Action: Pertuzumab binds to subdomain II of the extracellular dimerization domain of HER2, blocking ligand-dependent heterodimerization with other HER family members. This inhibits signaling through the MAP kinase and PI3K pathways, leading to growth arrest and apoptosis.
Receptor Binding: Binds specifically to HER2.
Enzyme Inhibition: Inhibits downstream signaling pathways like MAP kinase and PI3K.
Elimination Pathways: Primarily catabolism, with some renal elimination.
Dosage
Standard Dosage
Adults:
- Initial dose: 840 mg IV infusion over 60 minutes.
- Maintenance dose: 420 mg IV infusion over 30-60 minutes every 3 weeks.
- Phesgo (SC): 1200 mg/600 mg loading dose, followed by 600 mg/600 mg maintenance dose every 3 weeks.
Children: Safety and efficacy have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No dose adjustment necessary.
- Patients with Renal Impairment: No dose adjustment necessary for mild to moderate impairment. Not studied in severe renal impairment.
- Patients with Hepatic Dysfunction: Not formally studied; use with caution.
- Patients with Comorbid Conditions: Close monitoring for cardiac dysfunction is essential, especially in patients with pre-existing heart conditions or those receiving anthracyclines.
Clinical Use Cases
Pertuzumab’s use in intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations isn’t directly indicated. Its core applications are specifically for HER2-positive breast cancer.
Dosage Adjustments
No routine dose adjustments based on body weight, age, or gender are required. For missed doses, administer as soon as possible and resume the regular schedule. If more than 6 weeks have passed since the last dose, re-administer the loading dose.
Side Effects
Common Side Effects
Diarrhea, nausea, alopecia (hair loss), fatigue, rash, peripheral neuropathy (numbness/tingling), neutropenia (low white blood cell count), upper respiratory infections, sore mouth.
Rare but Serious Side Effects
Left ventricular dysfunction/heart failure, embryo-fetal toxicity (if used during pregnancy), hypersensitivity reactions (including fever, chills, difficulty breathing), pulmonary toxicity.
Long-Term Effects
Chronic heart problems (including heart failure) can occur with prolonged use.
Adverse Drug Reactions (ADR)
Cardiomyopathy, severe neutropenia, febrile neutropenia, severe hypersensitivity reactions.
Contraindications
Known hypersensitivity to pertuzumab.
Drug Interactions
Anthracyclines (increased risk of cardiotoxicity). Use with caution with other drugs that can prolong the QT interval.
Pregnancy and Breastfeeding
Pregnancy Safety Category: Pertuzumab can cause fetal harm and should be avoided during pregnancy. Effective contraception is necessary during treatment and for 7 months after the last dose.
Breastfeeding: Pertuzumab may pass into breast milk. Breastfeeding is not recommended during treatment and for 7 months after the last dose.
Drug Profile Summary
- Mechanism of Action: HER2 dimerization inhibitor, ADCC mediator.
- Side Effects: Diarrhea, nausea, alopecia, fatigue, rash, neuropathy, neutropenia, cardiotoxicity.
- Contraindications: Hypersensitivity to pertuzumab.
- Drug Interactions: Anthracyclines, QT prolonging drugs.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy; not recommended during breastfeeding.
- Dosage: 840 mg loading dose, then 420 mg every 3 weeks IV; Phesgo SC available.
- Monitoring Parameters: LVEF, complete blood count, signs of hypersensitivity or cardiotoxicity.
Popular Combinations
- Trastuzumab and docetaxel (for metastatic breast cancer)
- Trastuzumab and chemotherapy regimens (for early breast cancer)
Precautions
- Monitor cardiac function (LVEF) before, during, and after treatment.
- Monitor blood counts due to the risk of neutropenia.
- Patients should use effective contraception during treatment and for 7 months after the last dose.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pertuzumab?
A: 840 mg IV loading dose followed by 420 mg IV every 3 weeks. Phesgo (SC formulation): 1200 mg/600 mg loading dose, followed by 600 mg/600 mg maintenance dose every 3 weeks.
Q2: What are the most common side effects?
A: Diarrhea, nausea, alopecia, fatigue, rash, and peripheral neuropathy.
Q3: How does Pertuzumab work?
A: It inhibits HER2 dimerization, blocks downstream signaling, and promotes ADCC.
Q4: Can Pertuzumab be used during pregnancy?
A: No, it is contraindicated due to the risk of fetal harm.
Q5: What is the black box warning for Pertuzumab?
A: Left ventricular dysfunction and embryo-fetal toxicity.
Q6: What should be monitored during Pertuzumab treatment?
A: Cardiac function (LVEF), complete blood counts, and signs of hypersensitivity.
Q7: How is Pertuzumab administered?
A: Intravenous infusion (Perjeta) or subcutaneous injection (Phesgo).
Q8: What is the difference between Perjeta and Phesgo?
A: Perjeta is pertuzumab alone given intravenously. Phesgo combines pertuzumab with trastuzumab and hyaluronidase-zzfx for subcutaneous injection.
Q9: When should Pertuzumab be discontinued?
A: For confirmed clinically significant decline in left ventricular function, severe hypersensitivity reactions, or other unacceptable toxicities.
