Panitumumab (Monograph)

Brand name: Vectibix
Drug class: Antineoplastic Agents
- Epidermal Growth Factor Receptor Inhibitors
- EGFR Inhibitors
- EGF Receptor Inhibitors
VA class: AN900
Chemical name: Disulfide with human monoclonal ABX-EGF light chain anti-(human epidermal growth factor receptor) (human monoclonal ABX-EGF heavy chain) immunoglobulin dimer
Molecular formula: C₆₃₀₆H₉₇₃₂N₁₆₇₂O₁₉₉₄S₄₆
CAS number: 339177-26-3

Medically reviewed by Drugs.com on Aug 16, 2024. Written by ASHP.

Introduction

Antineoplastic agent; a recombinant human IgG₂ kappa monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR; also called an epidermal growth factor receptor [EGFR] inhibitor).^{1 2 3 4 5 6 7 8 9 13 14 22 31 35 37 42}

Uses for Panitumumab

Colorectal Cancer

Used as a single agent for the treatment of metastatic colorectal cancer that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens in adult patients with tumors that express EGFR.^{1 2 3 4 5 7 8 9 11 13 14 21 22 31 32 37}

Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for panitumumab in patients whose tumors had KRAS (also called K-ras) mutations in codon 12 or 13;^{1 33 44} ASCO⁴⁴ and some clinicians^{26 29 30 31 32 33} recommend that all patients with metastatic colorectal cancer who are potential candidates for EGFR inhibitor therapy (e.g., panitumumab, cetuximab) have their tumor tested for KRAS mutations^{26 29 30 31 32 33 44} in a Clinical Laboratory Improvement Amendments (CLIA)-accredited laboratory.⁴⁴ If KRAS mutation in codon 12 or 13 is detected, use of panitumumab is not recommended.^{1 44}

Efficacy of panitumumab monotherapy determined based on progression-free survival; actual clinical benefits (e.g., improvement in disease-related symptoms, increased survival) not adequately studied.^{1 13 37}

Available data do not support the use of panitumumab after clinical failure of cetuximab in metastatic colorectal cancer and some authorities do not recommend the use of either of these agents after clinical failure of the other.¹¹ However, panitumumab potentially may be used as an alternative to cetuximab therapy (e.g., if cetuximab is contraindicated or not tolerated).^{11 19 20}

Panitumumab is not approved for use in combination with chemotherapy for the treatment of metastatic colorectal cancer.¹ (See Use in Combination with other Chemotherapeutic Regimens under Cautions and Specific Drugs or Therapies under Interactions.)

Panitumumab Dosage and Administration

General

• Premedication to minimize the risk of infusion-related reactions does not appear to be necessary; however, appropriate medical resources for the treatment of severe reactions should be available during panitumumab infusions.^{1 7 8 9 15 19 22}

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.¹ Do not administer by rapid IV injection (e.g., IV push or “bolus”).¹

Solution should be colorless and may contain a small amount of visible, translucent-to-white, amorphous, proteinaceous particulates of panitumumab; do not administer if discoloration observed.¹

Do not shake vials.¹

Use infusion pump to administer.¹ Prior to and following administration, flush line with 0.9% sodium chloride injection.¹ Administer drug through a low-protein-binding 0.2- or 0.22-µm inline filter.¹

Dilution

Withdraw appropriate dose of panitumumab injection solution (containing 20 mg/mL) and dilute in 0.9% sodium chloride injection to a total volume of 100 mL; doses >1 g should be diluted in 0.9% sodium chloride injection to a total volume of 150 mL.¹ Final concentration should not exceed 10 mg of panitumumab per mL.¹

Mix diluted solution by gentle inversion; do not shake.¹

Do not mix or dilute panitumumab with other drugs or infusion solutions.¹

Rate of Administration

Administer over 60 minutes if dose is ≤1 g; administer over 90 minutes if dose is >1 g.¹

Dosage

Adults

Colorectal Cancer

IV

For the management of previously treated, EGFR-expressing metastatic colorectal cancer as monotherapy, 6 mg/kg over 60 minutes every 14 days.^{1 2 4 9 13} Doses >1 g should be infused over 90 minutes.^{1 2 9} In the randomized controlled trial evaluating panitumumab monotherapy for metastatic colorectal cancer, a median of 5 doses was administered.¹

Dosage Modification for Toxicity

Infusion-related Reactions

If mild or moderate (grade 1 or 2) infusion-related reactions occur, reduce infusion rate by 50% for the duration of that infusion.^{1 9}

If severe (grade 3 or 4) infusion-related reactions occur, discontinue therapy immediately and permanently.^{1 9 15}

Dermatologic Toxicity

If severe (grade 3 or 4) or intolerable dermatologic toxicity occurs, withhold therapy.¹ If toxicity does not improve to ≤ grade 2 within 1 month, permanently discontinue therapy.¹

If dermatologic toxicity improves to ≤ grade 2 and patient is symptomatically improved after withholding no more than 2 doses, resume treatment at 50% of the original dosage.¹ Dosage may then be increased in increments of 25% of the original dosage up to the recommended dosage of 6 mg/kg if toxicity does not recur.¹ If toxicity recurs, permanently discontinue therapy.¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Panitumumab

Contraindications

• None known.¹

Warnings/Precautions

Warnings

Dermatologic, Mucosal, and Ocular Toxicity

Dermatologic toxicity, which may affect the skin, mucosa, eyes, and/or nails, was reported in approximately 90% of patients and was severe (grade 3 or 4) in 16% of patients in a large, controlled trial.^{1 3 9 12 13 14 16 43} Manifested as dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and/or skin fissures.^{1 12 13 14 43} Severe dermatologic toxicity may result in infectious complications, including sepsis, septic death, and abscesses requiring incision and drainage.^{1 12}

Mucosal toxicity, including oral mucositis and stomatitis, reported in 6–7% of patients receiving panitumumab therapy; one case of grade 3 mucosal inflammation reported.¹

Ocular toxicity, including conjunctivitis, ocular hyperemia, increased lacrimation, and eye/eyelid irritation, reported in 15% of patients.^{1 9 14}

Paronychia reported in 25% of patients receiving panitumumab, with severe cases (grade 3 or 4) reported in 2%; other nail disorders reported in 9% of patients.^{1 12 13}

Median time to development of dermatologic and ocular toxicity was 14 days and median time to most severe toxicity was 15 days after the first dose of panitumumab; median time to resolution after the last dose of panitumumab was 84 days.¹

Withhold panitumumab for severe or life-threatening dermatologic toxicity.¹ If severe adverse dermatologic effects occur, monitor patients for possible inflammatory or infectious complications and initiate appropriate therapy.^{1 12 14} Prevention and treatment should be carefully individualized and may require specialized care; topical and/or systemic antibiotics, topical emollients, topical corticosteroids, and/or systemic antihistamines may be helpful in some cases.^{7 12 14 41 43} Dosage modifications, including possible discontinuance of therapy, may be required.^{1 12 14} (See Dermatologic Toxicity in Boxed Warning and under Dosage and Administration.)

Infusion-related Reactions

Infusion-related reactions occurred in 4% and severe reactions (grade 3 or 4) occurred in 1% of patients receiving panitumumab in the monotherapy clinical trial (designated Study 1 by the manufacturer).^{1 14} In all clinical studies, severe infusion reactions occurred in approximately 1% of the panitumumab-treated patients.¹ Serious infusion reactions included anaphylactic reactions, bronchospasm, and hypotension.¹ No fatalities were reported; however, fatalities have occurred with other monoclonal antibody products.¹ A reduction in infusion rate or discontinuance of therapy may be necessary depending on severity of the reaction.¹ (See Infusion-related Reactions in Boxed Warning and under Dosage and Administration.)

Pulmonary Effects

Pulmonary fibrosis (including 2 fatalities; 1 case occurred in a patient with preexisting idiopathic pulmonary fibrosis) reported in <1% of patients receiving panitumumab.¹ Use with caution in patients with preexisting lung disease; such patients were excluded from clinical trials.^{1 24} Permanently discontinue panitumumab in patients who develop interstitial lung disease, pneumonitis, or lung infiltrates during therapy.¹

Other Warnings and Precautions

Use in Combination with other Chemotherapeutic Regimens

Panitumumab is not indicated for use in combination with chemotherapy.¹

In a large, randomized, open-label, multicenter trial, addition of panitumumab to a bevacizumab plus chemotherapy regimen (containing either oxaliplatin or irinotecan and fluorouracil) in the first-line treatment of metastatic colorectal cancer resulted in poorer outcomes (i.e., decreased overall survival) and increased toxicity (e.g., higher incidence of grade 3–5 adverse reactions).^{1 18 27 39} Grade 3/4 adverse reactions occurred more frequently in panitumumab-treated patients compared with those in non-panitumumab-containing treatment arms and included dermatologic toxicity (e.g., rash, acneiform dermatitis), diarrhea, dehydration (mainly in patients with diarrhea), hypokalemia, stomatitis or mucositis, and hypomagnesemia.^{1 18 27 39} Grade 3–5 pulmonary embolism also occurred more frequently in panitumumab-treated patients compared with non-panitumumab-containing treatment arms (7% and 4%, respectively).^{1 18 27 39} Because of the toxicities experienced, patients randomized to panitumumab, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each agent (oxaliplatin, irinotecan, bolus fluorouracil, and/or infusional fluorouracil) over the first 24 weeks compared with those receiving bevacizumab plus chemotherapy.¹

In another clinical study, addition of panitumumab to the irinotecan, direct IV injection (“bolus”) fluorouracil, and leucovorin (IFL) regimen resulted in an increased incidence and severity of chemotherapy-induced diarrhea (58% incidence of grade 3/4 diarrhea; one fatal case of grade 5 diarrhea).^{1 17} Grade 3 diarrhea reported in 25% of patients receiving panitumumab plus irinotecan, continuous fluorouracil infusion, and leucovorin (FOLFIRI).^{1 17}

Severe diarrhea and dehydration, which may lead to acute renal failure and other complications, observed in patients receiving panitumumab in combination with chemotherapy.^{1 16 17} (See Specific Drugs or Therapies under Interactions.)

Pulmonary Effects

Pulmonary fibrosis (including 2 fatalities; 1 case occurred in a patient with preexisting idiopathic pulmonary fibrosis) reported in <1% of patients receiving panitumumab.¹ Use with caution in patients with preexisting lung disease; such patients were excluded from clinical trials.^{1 24} Permanently discontinue panitumumab in patients who develop interstitial lung disease, pneumonitis, or lung infiltrates during therapy.¹

Electrolyte Effects

Electrolyte abnormalities, including decreased serum magnesium concentrations, reported.^{1 9 13 14 22} Grade 3 or 4 hypomagnesemia requiring oral or IV electrolyte repletion occurred in 2% of patients in one study.^{1 13} In some patients, both hypomagnesemia and hypocalcemia occurred.¹ Hypomagnesemia usually occurred ≥6 weeks following initiation of panitumumab therapy.¹

Monitor serum electrolytes (including magnesium and calcium) periodically during and for 8 weeks following completion of panitumumab therapy.^{1 22}

Institute appropriate treatment (e.g., oral or IV electrolyte repletion) if necessary.^{1 13}

Photosensitivity

Exposure to sunlight can exacerbate dermatologic toxicity; the manufacturer recommends that patients apply sunscreen, wear hats, and limit sun exposure during therapy and for 2 months following the last dose of the drug.^{1 7 12 16}

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryolethality and abortifacient effects demonstrated in animals.^{1 16} No studies to date in pregnant women.¹ Avoid pregnancy during panitumumab therapy and for 6 months after the last dose.^{1 16} If used during pregnancy or patient becomes pregnant while receiving the drug, apprise of potential fetal hazard and/or risk for loss of the pregnancy.¹ (See Advice to Patients.)

EGFR Testing

The manufacturer states that pretreatment assessment for EGFR expression is necessary for selecting appropriate patients for panitumumab therapy.^{1 23 24} However, panitumumab has demonstrated antitumor activity in patients with low or negative EGFR levels.^{4 24 25} Some authorities state that routine EGFR expression testing is not recommended and that patients should not be included or excluded from panitumumab therapy based solely on EGFR test results.¹¹

If testing is conducted, EGFR expression should be assessed by laboratories with demonstrated proficiency in the specific technology being utilized.¹ Improper assay performance may lead to unreliable results.¹

Immunologic Effects

Appears to have relatively low immunogenic potential.^{1 13} Anti-panitumumab antibodies detected in ≤4.6% of panitumumab-treated patients using the acid dissociation ELISA and Biacore screening immunoassays.¹ In patients whose sera tested positive in screening bioassays, neutralizing antibodies detected in ≤1.6% of samples using an in vitro biological assay.¹ No known relationship between appearance of antibodies and the pharmacokinetic or tolerability profile of panitumumab.¹

Specific Populations

Pregnancy

Category C.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Amgen's Pregnancy Surveillance Program: 800-772-6436.¹

Lactation

IgG distributed into human milk; published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts.¹ Discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.¹ If nursing is interrupted, based on the mean half-life of panitumumab, nursing should not be resumed earlier than 2 months following the last dose of panitumumab.^{1 16}

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.^{1 16 24}

Geriatric Use

In the randomized, controlled study, 42% of the patients with metastatic colorectal cancer who received panitumumab were ≥65 years of age.¹ Although the clinical study of panitumumab did not include a sufficient number of geriatric patients to determine whether they respond differently than younger patients, no apparent differences in safety and efficacy relative to younger adults were reported.^{1 13}

Common Adverse Effects

Monotherapy or combination therapy in patients with colorectal cancer: Dermatological effects (e.g., erythema, acne or acneiform dermatitis, pruritus, skin exfoliation, rash, skin fissures, dry skin),^{1 3 9 12 13 14 16 43} hypomagnesemia,^{1 9 13 14 22} paronychia and other nail disorders,^{1 9 12 13 14} fatigue,^{1 9 13 14 16} GI effects (e.g., abdominal pain, nausea, constipation, diarrhea),^{1 9 13 14 16} stomatitis or oral mucositis,¹ dehydration,^{1 9} peripheral edema,^{1 13 14} cough,^{1 13 14} and ocular toxicity (e.g., conjunctivitis, increased lacrimation, ocular hyperemia, eye/eyelid irritation).^{1 9 14}

Drug Interactions

No formal drug interaction studies have been performed.^{1 16}

Specific Drugs or Therapies

Panitumumab Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics are nonlinear following single-dose administration, with AUC increasing in a greater than dose-proportional manner and clearance decreasing with increasing doses; however, at doses >2 mg/kg, AUC increases in an approximately dose-proportional manner.^{8 1}

Plasma Concentrations

Peak and trough plasma concentrations at steady-state (reached by 3rd infusion after 4 weeks) approximately 213 and 39 mcg/mL, respectively.¹

Distribution

Extent

Human IgG crosses the placenta and is distributed into milk.¹ Potential exists for panitumumab to cross the placenta.¹ Although not known, panitumumab possibly distributed into milk.¹

Elimination

Metabolism

Metabolism not fully understood.²⁴

Elimination Route

Systemic clearance believed to be through internalization of panitumumab-EGFR complex and via the reticuloendothelial system.^{2 8 9 24}

Half-life

Approximately 7.5 days (range: 3.6–10.9 days) following multiple dosing.^{1 8}

Stability

Storage

Parenteral

Injection

2–8°C.¹ Protect from direct sunlight; do not freeze.¹ Discard any unused portion.¹

Diluted infusion solutions are stable for up to 6 hours if stored at room temperature or for up to 24 hours if stored at 2–8°C.¹ Do not freeze.¹

Compatibility

Parenteral

Solution Compatibility

Actions

• Antineoplastic agent; a recombinant human IgG₂ kappa monoclonal antibody that binds to human EGFR.^{1 2 3 4 5 6 7 8 9 13 14 22} An immunoglobulin containing a fully human framework.^{1 2 3 5 6 7 8}

• Panitumumab binds specifically to EGFR (HER1, c-erbB-1) on both normal and tumor cells and competitively blocks cellular action of EGF and other ligands (e.g., transforming growth factor [TGF]-α).^{1 2 3 5 6 7 8}

• Interaction of EGFR with its normal ligands (e.g., EGF, TGF-α) results in phosphorylation and activation of a series of intracellular proteins that, in turn, regulate transcription of genes involved with cellular growth and survival, motility, and proliferation.¹ Signal transduction through EGFR leads to activation of the wild-type (nonmutated) KRAS gene.¹ However, the presence of an activating somatic mutation of the KRAS gene (mutated KRAS) in a cancer cell can lead to dysregulation of signaling pathways and resistance to EGFR inhibitor therapy (e.g., cetuximab, panitumumab).^{1 33}

• Binding of panitumumab to EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis (programmed cell death), decreased proinflammatory cytokine and vascular endothelial growth factor production, and internalization of the EGFR.^{1 2 5 6}

• In vitro tests and in vivo animal studies suggest that panitumumab may inhibit growth and survival of tumor cells that overexpress EGFR.^{1 2 5 6 31}

Advice to Patients

• Risk of adverse dermatologic effects, infusion-related reactions (e.g., fever, chills, or breathing problems), pulmonary fibrosis, and potential embryofetal lethality.^{1 12 13 16 17}

• Importance of informing patients to report persistent or recurrent coughing, wheezing, dyspnea, or new onset facial swelling.¹

• Importance of informing patients to report diarrhea and dehydration to a healthcare professional.¹

• Importance of informing patients to report skin, ocular or visual changes to a healthcare professional.^{1 16}

• Importance of informing patients to use sunscreen and hats and limit sun exposure during therapy and for 2 months following the last dose of the drug to avoid exacerbation of adverse dermatologic effects.^{1 7 12 17}

• Importance of advising patients that periodic monitoring of serum electrolytes (including magnesium and calcium) is required.^{1 16 22}

• Necessity of advising men and women to use an effective method of contraception during panitumumab therapy and for 6 months following the last dose of the drug; women should avoid breast-feeding during therapy and for 2 months following discontinuance of the drug.^{1 16} Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; panitumumab may affect ability of women to become pregnant.^{1 16} If pregnancy occurs, advise patient of risk to the fetus and/or the potential risk for loss of the pregnancy.^{1 16}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses, particularly pulmonary disease.^{1 16}

• Importance of informing patients of other important precautionary information.^{1 16} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Biological Products Related to panitumumab

Find detailed information on biosimilars for this medication.

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