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: IV: 6 mg/kg every 14 days as a single agent (Van Cutsem 2007) or in combination with FOLFOX (fluorouracil, leucovorin, and oxaliplatin) (Douillard 2010; Douillard 2013); continue until disease progression or unacceptable toxicity (Douillard 2010; Van Cutsem 2007).
Colorectal cancer, metastatic, RAS wild-type 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 (Peeters 2010).
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 (has not been studied).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Refer to adult dosing.
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 (ASCO [Griggs 2021]).
Infusion reactions, mild-to-moderate (grade 1 or 2): Reduce the infusion rate by 50% for the duration of infusion.
Infusion reactions, severe (grade 3 or 4): Stop infusion; consider permanent discontinuation (depending on severity or persistence of reaction).
Dermatologic 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.
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
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 patients with 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)
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.
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: [US Boxed Warning]: Dermatologic toxicities have been reported in 90% of patients receiving single agent panitumumab and were severe (grade 3 or higher) in 15% of patients; may include 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 2 weeks, with resolution ~12 weeks after discontinuation. 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). Monitor all dermatologic toxicities for development of inflammation or infection. Rare cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported; bullous mucocutaneous disease (life-threatening/fatal) have been observed. Withhold treatment for severe or life-threatening dermatologic or soft tissue toxicities associated with severe/life-threatening inflammatory or infectious complications; dermatologic toxicity may require dose reduction or permanent discontinuation. Patients should minimize sunlight exposure and wear sunscreen and protective clothing/hat; sunlight may exacerbate skin reactions. Nail toxicity has also been reported.
• 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. Gastric mucosal toxicity has also been reported.
• Electrolyte depletion: Magnesium and/or calcium depletion may occur during treatment (may be delayed; hypomagnesemia occurred ≥8 weeks after completion of panitumumab) and after treatment is discontinued; electrolyte repletion may be necessary. Monitor for hypomagnesemia and hypocalcemia during treatment and for at least 8 weeks after completion. 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. Discontinue infusion for severe reactions; permanently discontinue in patients with persistent severe infusion reactions. Appropriate medical support for the management of infusion reactions should be readily available. Mild to moderate infusion reactions are managed by slowing the infusion rate.
• 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. Interrupt treatment for acute onset or worsening of pulmonary symptoms; permanently discontinue treatment if interstitial lung disease is confirmed. 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. Panitumumab is not indicated in patients with RAS mutation-positive metastatic colorectal cancer or patients in whom RAS mutation status is unknown. Utilizing an anti-EGFR-directed antibody in patients whose tumors contain RAS mutations resulted in increased toxicity without clinical benefit. In a study of FOLFOX4 (fluorouracil, leucovorin, and oxaliplatin) ± panitumumab, patients with a KRAS mutation who received panitumumab with FOLFOX4 experienced a significantly shortened progression-free survival (Douillard 2010). In addition, a subset analysis of patients with wild-type KRAS identified additional RAS (KRAS [exons 3 and 4] or NRAS [exons 2, 3, 4]) mutations; progression-free survival and overall survival were significantly shortened in patients with RAS mutations who received FOLFOX4 in combination with panitumumab (Douillard 2013). The American Society of Clinical Oncology (ASCO) provisional clinical opinion update recommends 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 (Allegra 2016). 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.
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 at least 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 establish RAS mutation status and 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 for skin toxicity, for evidence of ocular toxicity, 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.
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)
Solution (Vectibix Intravenous)
100 mg/5 mL (per mL): $355.68
400 mg/20 mL (per mL): $355.68
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