Version May 2024
Dermatologic toxicities occurred in 90% of patients and were severe (National Cancer Institute Common Toxicity Criteria [NCI-CTC] grade 3 and higher) in 15% of patients receiving panitumumab monotherapy.
Note: Establish RAS mutation status (to confirm RAS wild-type) prior to treatment initiation.
Colorectal cancer, metastatic, RAS wild-type:
Single agent therapy: IV: 6 mg/kg every 14 days; continue until disease progression or unacceptable toxicity (Ref).
In combination with CAPOX (capecitabine and oxaliplatin; off-label combination): IV: 9 mg/kg every 21 days for at least 6 cycles or until disease progression or unacceptable toxicity (Ref).
In combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin): IV: 6 mg/kg every 14 days; continue until disease progression or unacceptable toxicity (Ref). Note: Data from a phase 3 randomized, multicenter trial showed significantly improved overall survival in patients with previously untreated RAS wild-type and left-sided metastatic colorectal cancer who received panitumumab in combination with mFOLFOX6 versus bevacizumab in combination with mFOLFOX6 (Ref).
In combination with FOLFIRI (fluorouracil, leucovorin, and irinotecan; off-label combination): IV: 6 mg/kg every 14 days; continue until disease progression or unacceptable toxicity (Ref).
In combination with FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan; off-label combination): IV: 6 mg/kg every 14 days until disease progression or resection for up to a maximum of 12 preoperative cycles; after resection, patients received the same regimen as adjuvant therapy for a total of 12 perioperative cycles (Ref).
As maintenance therapy (in combination with fluorouracil and leucovorin) following 6 cycles of FOLFOX plus panitumumab; off-label combination): IV: 6 mg/kg every 14 days; continue until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, no need for dosage adjustment is expected (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. The following adjustments have been recommended:
Mild or moderate impairment: No dosage adjustment is needed (Ref).
Severe impairment: No need for dosage adjustment is expected (Ref).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Electrolyte depletion: Replete as clinically appropriate.
Infusion reactions:
Mild to moderate (grade 1 or 2): Reduce the infusion rate by 50% for the duration of infusion.
Severe (grade 3 or 4): Stop infusion; consider permanent discontinuation (depending on severity or persistence of reaction).
Dermatologic or soft tissue toxicity:
Grade 3 toxicity (first occurrence): Withhold 1 to 2 doses; if reaction improves to <grade 3, resume therapy at initial dose.
Grade 3 toxicity (second occurrence): Withhold 1 to 2 doses; if reaction improves to <grade 3, resume therapy at 80% of initial dose.
Grade 3 toxicity (third occurrence): Withhold 1 to 2 doses; if reaction improves to <grade 3, resume therapy at 60% of initial dose.
Grade 3 toxicity (fourth occurrence), grade 3 toxicity that does not recover to <grade 3 after withholding 1 or 2 doses, or grade 4 toxicity: Permanently discontinue.
Ocular toxicity (acute or worsening keratitis, ulcerative keratitis, or corneal perforation): Interrupt or discontinue treatment.
Pulmonary toxicity:
Acute onset or worsening pulmonary symptoms: Interrupt treatment.
Interstitial lung disease: Permanently discontinue treatment.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Dermatologic: Acne vulgaris (14%), acneiform eruption (57%), erythema of skin (66%), exfoliative dermatitis (18%), paronychia (25%), pruritus (58%), skin fissure (20%), skin rash (22%), skin toxicity (90%; severe dermatological reaction: 15%)
Gastrointestinal: Nausea (23%; grade 3/4: <1%), diarrhea (21%; grades 3/4: 2%), vomiting (19%; grade 3/4: 3%)
Nervous system: Fatigue (26%)
Ophthalmic: Ocular toxicity (16%)
Respiratory: Cough (15%), dyspnea (18%)
Miscellaneous: Fever (17%)
1% to 10%:
Cardiovascular: Pulmonary embolism (1%)
Dermatologic: Dermal ulcer (6%), desquamation (9%), nail disease (10%), papular rash (2%), pustular rash (4%), xeroderma (10%)
Endocrine & metabolic: Dehydration (3%), hypomagnesemia (grades 3/4: 7%)
Gastrointestinal: Mucosal swelling (inflammation: 7%), stomatitis (7%), xerostomia (5%)
Immunologic: Antibody development (≤5%; neutralizing: <1%)
Nervous system: Chills (3%)
Ophthalmic: Abnormal eyelash growth (6%), conjunctivitis (5%)
Respiratory: Epistaxis (4%), interstitial pulmonary disease (1%)
Miscellaneous: Infusion related reaction (3% to 4%; severe infusion reaction: ≤1%)
<1%: Respiratory: Pulmonary fibrosis
Frequency not defined:
Endocrine & metabolic: Hypokalemia
Gastrointestinal: Intestinal obstruction
Postmarketing:
Dermatologic: Bullous skin disease (mucocutaneous), skin necrosis
Hypersensitivity: Angioedema
Ophthalmic: Corneal perforation, corneal ulcer, keratitis (including ulcerative)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: History of severe or life-threatening hypersensitivity reactions to panitumumab or any component of the formulation.
Concerns related to adverse effects:
• Dermatologic toxicity: Dermatologic toxicities have been reported in most patients receiving single agent panitumumab; severe (≥ grade 3) reactions have occurred; manifestations included dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Severe skin toxicities may be complicated by infection, sepsis, necrotizing fasciitis, or abscesses. The median time to development of skin (or ocular) toxicity was 12 days, with resolution ~14 weeks. The severity of dermatologic toxicity is predictive for response; grades 2 to 4 skin toxicity correlates with improved progression free survival and overall survival, compared to grade 1 skin toxicity (Peeters 2009; Van Cutsem 2007). Rare cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported; bullous mucocutaneous disease (life-threatening/fatal) have been observed. Patients should minimize sunlight exposure and wear sunscreen and protective clothing/hat; sunlight may exacerbate skin reactions.
• Diarrhea: May cause diarrhea; the incidence and severity of chemotherapy-induced diarrhea is increased with combination chemotherapy. Severe diarrhea and dehydration (which may lead to acute renal failure) has been observed with panitumumab in combination with chemotherapy.
• Electrolyte depletion: Magnesium and/or calcium depletion may occur during treatment; may be delayed. Hypomagnesemia occurred during and for up to 8 weeks after completion of panitumumab treatment. Hypokalemia has also been reported.
• Infusion reactions: Severe infusion reactions (bronchospasm, dyspnea, fever, chills, and hypotension) have been reported in ~1% of patients; fatal infusion reactions have been reported with postmarketing surveillance. Appropriate medical support for the management of infusion reactions should be readily available.
• Ocular toxicity: Keratitis, ulcerative keratitis, and corneal perforation have occurred.
• Pulmonary toxicity: Pulmonary fibrosis and interstitial lung disease have been observed (rarely) in clinical trials; fatalities have been reported. Patients with a history of or evidence of interstitial pneumonitis or pulmonary fibrosis were excluded from most clinical trials; consider the benefits of therapy versus the risk of pulmonary complications in such patients.
Disease-related concerns:
• Colorectal cancer and RAS mutation status: Confirm absence of RAS mutation prior to treatment; patients with codons 12 and 13 (exon 2), codons 59 and 61 (exon 3), or codons 117 and 146 (exon 4) RAS (KRAS or NRAS) mutations are unlikely to benefit from EGFR inhibitor therapy. The American Society of Clinical Oncology (ASCO) provisional clinical opinion update, as well as a guideline for molecular biomarkers for the evaluation of colorectal cancer, recommend that all patients with metastatic colorectal cancer who are candidates for anti-EGFR therapy should be tested (in a certified lab) for mutations in both KRAS and NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146); anti-EGFR monoclonal antibody therapy should only be considered in patients whose tumors lack mutations after extended RAS testing (ASCO [Allegra 2016]; ASCP/CAP/AMP/ASCO [Sepulveda 2017]). Information on tests approved for detection of RAS mutation is available at www.fda.gov/CompanionDiagnostics. Panitumumab is also reported to be ineffective in patients with BRAF V600E mutation (Di Nicolantonio 2008).
Concurrent drug therapy issues:
• Bevacizumab and combination chemotherapy: In a study of bevacizumab with combination chemotherapy ± panitumumab, the use of panitumumab resulted in decreased progression-free and overall survival and significantly increased toxicity compared to regimens without panitumumab (Hecht 2009). Toxicities included rash/acneiform dermatitis, diarrhea/dehydration, electrolyte disturbances, mucositis/stomatitis, and an increased incidence of pulmonary embolism.
Special populations:
• Older adult: Patients >65 years of age receiving panitumumab plus FOLFOX experienced a higher incidence of serious adverse events including severe diarrhea.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Vectibix: 100 mg/5 mL (5 mL); 400 mg/20 mL (20 mL)
No
Solution (Vectibix Intravenous)
100 mg/5 mL (per mL): $395.50
400 mg/20 mL (per mL): $395.50
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Vectibix: 100 mg/5 mL (5 mL); 400 mg/20 mL (20 mL)
IV: For IV infusion only; do not administer IV push or as a bolus. Administer via infusion pump through a low protein-binding 0.2 or 0.22 micrometer in-line filter. Doses ≤1,000 mg, infuse over 1 hour; if first infusion is tolerated, subsequent doses may be administered over 30 to 60 minutes. Doses >1,000 mg, infuse over 90 minutes. Flush line with NS before and after infusion; do not mix or administer with other medications. Reduce infusion rate by 50% for mild to moderate infusion reactions (grades 1 and 2); stop infusion for severe infusion reactions (grades 3 and 4) and consider permanent discontinuation. Appropriate medical support for the management of infusion reactions should be readily available.
Colorectal cancer, metastatic: Treatment of wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an approved test) metastatic colorectal cancer (mCRC), either as first-line therapy in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or as a single agent following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy
Limitations of use: Panitumumab is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.
Colorectal cancer, metastatic, KRAS wild-type (in combination with other chemotherapy agents); Cutaneous squamous cell carcinoma, unresectable, advanced or metastatic
Panitumumab may be confused with pembrolizumab, pertuzumab, polatuzumab vedotin
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Patients who could become pregnant should use effective contraception during treatment and for 2 months after the dose of panitumumab.
Based on animal reproduction studies and on the mechanism of action, panitumumab may cause fetal harm if administered during pregnancy. Panitumumab is a humanized monoclonal antibody (IgG2). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
It is not known if panitumumab is present in breast milk. Panitumumab is an IgG monoclonal antibody and maternal IgG immunoglobulins are excreted in breast milk; however, breast milk antibodies are not expected to enter neonatal and infant circulation in substantial amounts. Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends patients not breastfeed during therapy and for 2 months after the final panitumumab dose.
RAS genotyping of tumor tissue to confirm RAS wild-type (prior to treatment initiation). Monitor serum electrolytes, including magnesium and calcium (periodically during and for at least 8 weeks after therapy), and potassium. Monitor vital signs and temperature before, during, and after infusion. Monitor all dermatologic toxicities for development of inflammation or infection, for evidence of ocular toxicity (eg, keratitis, ulcerative keratitis, or corneal perforation), and for acute onset or worsening pulmonary symptoms.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]).
Panitumumab is a recombinant human IgG2 monoclonal antibody which binds specifically to the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) and competitively inhibits the binding of epidermal growth factor (EGF) and other ligands. Binding to the EGFR blocks phosphorylation and activation of intracellular tyrosine kinases, resulting in inhibition of cell survival, growth, proliferation, and transformation. EGFR signal transduction may result in KRAS and NRAS wild-type activation; cells with RAS mutations appear to be unaffected by EGFR inhibition.
Half-life elimination: ~7.5 days (range: 4 to 11 days)
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