Panitumumab, 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), is an antineoplastic agent.1
Panitumumab is used in combination with FOLFOX chemotherapy as first-line treatment in adults with wild-type RAS metastatic colorectal cancer (mCRC) (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test).1 Panitumumab is also used as monotherapy in adults for the treatment of wild-type RAS mCRC that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.1
Panitumumab is used in combination with sotorasib for the treatment of adults with KRAS G12C-mutated mCRC, as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy.1
Panitumumab does not demonstrate efficacy in the treatment of patients with RAS-mutant mCRC (which is defined as a RAS mutation in exon 2 [codons 12 and 13], exon 3 [codons 59 and 61], or exon 4 [codons 117 and 146] of KRAS and NRAS) except when used in combination with sotorasib in KRAS G12C-mutated mCRC.1 Panitumumab is also not indicated for patients with mCRC whose RAS mutation status has not been determined.1
Wild-type RAS Metastatic Colorectal Cancer
Recurrent or Refractory mCRC : The safety and efficacy of panitumumab in recurrent or refractory mCRC were established across 3 open-label, randomized, multinational studies: Study 20020408, which included 463 patients with epidermal growth factor receptor (EGFR)-expressing mCRC; Study 20080763, an open-label, multicenter trial enrolling 1010 patients with wild type KRAS mCRC; and Study 20100007, an open-label, multicenter study involving 377 patients with wild type KRAS mCRC.1
Patients enrolled in Study 20020408 were required to have immunohistochemical evidence of EGFR expression (using the DAKO EGFR pharmDx® test kit).1, 13, 37 In this trial, 463 patients with mCRC whose disease had progressed during or following treatment with a regimen containing a fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive panitumumab 6 mg/kg administered by IV infusion once every 2 weeks plus best supportive care or best supportive care alone until disease progression or unacceptable toxicity.1, 13 Patients randomized to best supportive care alone were eligible to cross over to panitumumab therapy upon disease progression.1, 13
Mean progression-free survival was longer in patients receiving panitumumab combined with best supportive care (96 days) compared with those receiving best supportive care alone (60 days).1, 13, 37 The panitumumab-treated patients also had a 46% lower relative progression rate compared with those receiving best supportive care alone.13 About 75% of patients randomized to best supportive care alone crossed over to panitumumab therapy following disease progression; the median time to crossover was 8.4 weeks.1, 37 A partial response was reported in 19 patients for an overall response rate of 8% in patients receiving panitumumab combined with best supportive care; no patient receiving best supportive care alone had an objective response.1, 37 The median duration of response in patients demonstrating a partial response was 17 weeks.1, 13, 37 No difference in overall survival was observed between the 2 treatment groups.1, 13, 37
Study 20080763 (the ASPECCT study) was a randomized, open‑label, phase 3, non‑inferiority trial that compared panitumumab with cetuximab in patients with chemotherapy‑refractory mCRC harboring wild‑type KRAS exon 2 tumors.1, 45 A total of 1010 patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-2 who had progressed on or were intolerant to standard fluoropyrimidine-, irinotecan‑, and oxaliplatin‑based chemotherapy were randomized to receive panitumumab (6 mg/kg IV every 2 weeks) or cetuximab (400 mg/m² IV loading dose on day 1 followed by 250 mg/m² IV weekly) until disease progression or unacceptable toxicity.1, 45 The primary endpoint was overall survival.1, 45 Panitumumab met the predefined non‑inferiority criterion, demonstrating overall survival comparable to cetuximab; median overall survival was 10.4 months with panitumumab and 10.0 months with cetuximab.1, 45 Progression‑free survival and objective response rates were also similar between treatment groups.1, 45
Study 20100007 was a randomized, open-label, phase 3 trial that evaluated panitumumab plus best supportive care versus best supportive care alone in patients with chemotherapy refractory mCRC with wild type KRAS exon 2 tumors.1, 46 A total of 377 patients with ECOG performance status 0-2 who progressed on standard fluoropyrimidine-, irinotecan-, and oxaliplatin-based therapy were randomized to receive panitumumab (6 mg/kg every 2 weeks) plus best supportive care or best supportive care alone; on-study crossover was not permitted.1, 46 The primary endpoint was overall survival.1, 46 Panitumumab plus best supportive care substantially improved overall survival compared with best supportive care alone, with a median overall survival of 10.0 months versus 7.4 months, respectively.1, 46 Among patients with RAS wild type mCRC, median overall survival was 10.0 months with panitumumab plus best supportive care compared with 6.9 months with best supportive care alone.1, 46 No clinical benefit from panitumumab was observed in patients with wild type KRAS exon 2 mCRC with other activating RAS mutations.46
Combination with FOLFOX Chemotherapy : Study 20050203 (the PRIME study) was a global, randomized, open- label, phase 3 trial that evaluated panitumumab in combination with FOLFOX4 versus FOLFOX4 alone as first line therapy in patients with mCRC.1, 47 A total of 1183 patients with ECOG performance status 0-2 were included; efficacy analyses were conducted by KRAS status.47 Panitumumab was administered at a dosage of 6 mg/kg IV as a 60 minute infusion prior to chemotherapy.1 The FOLFOX4 regimen included oxaliplatin 85 mg/m² IV and leucovorin 200 mg/m² IV given concurrently on day 1, followed by a 5-fluorouracil (5-FU) 400 mg/m² IV bolus and a 22 hour continuous IV infusion of 5-FU 600 mg/m²; leucovorin and 5-FU IV bolus and infusion were repeated on day 2.1 Medication regimens were given every 2 weeks.1, 47
The primary efficacy endpoint was progression-free survival in patients with wild type KRAS mCRC, with overall survival and objective response rate evaluated as key secondary endpoints.1, 47 In this population, panitumumab plus FOLFOX4 substantially improved progression-free survival compared with FOLFOX4 alone (median 9.6 versus 8 months, respectively).1
An exploratory overall survival analysis incorporating updated data from 82% of patients with wild type KRAS mCRC evaluated the effect of panitumumab plus FOLFOX4 compared with FOLFOX4 alone.1, 47 Among 325 patients treated with panitumumab plus FOLFOX4, median overall survival was 23.8 months, compared with 19.4 months among 331 patients who received FOLFOX4 alone.1
In retrospective exploratory analyses of the RAS wild type population, extended RAS testing was performed in 620 of 656 patients with wild type KRAS exon 2 mCRC using bidirectional Sanger sequencing and Surveyor/WAVE analysis.1 Approximately 17% of tumors harbored mutations in KRAS exons 3 or 4 or NRAS exons 2, 3, or 4.1
KRAS G12C-Mutated Metastatic Colorectal Cancer
The CodeBreaK 300 study was a randomized, open‑label, phase 3 trial evaluating panitumumab in combination with sotorasib in patients with previously treated mCRC harboring a KRAS G12C mutation.1, 48 Eligible patients were adults (≥18 years of age) who had received at least one prior line of therapy for mCRC and had previously been treated with a fluoropyrimidine, oxaliplatin, and irinotecan for metastatic disease, unless contraindicated.1, 48 All patients were required to have centrally-confirmed KRAS G12C-mutated mCRC identified prospectively in tumor tissue using the QIAGEN therascreen® KRAS RGQ PCR assay.1, 48 Additional eligibility criteria included an ECOG performance status of 0-2 and at least one measurable lesion.1, 48
A total of 160 patients were randomized to receive panitumumab 6 mg/kg IV every 2 weeks in combination with sotorasib 960 mg orally once daily, panitumumab plus sotorasib 240 mg once daily, or an investigator's choice of standard of care consisting of trifluridine/tipiracil or regorafenib.1, 48 Randomization was stratified by prior anti-angiogenic therapy, time from initial diagnosis of metastatic disease (<18 versus ≥18 months), and ECOG performance status (0-1 versus 2).1, 48
The primary efficacy endpoint was progression-free survival, and secondary endpoints included overall survival, objective response rate, and duration of response.1, 48 Efficacy analyses focused on the recommended sotorasib dose of 960 mg daily in combination with panitumumab.1, 48 Median progression-free survival was longer with sotorasib 960 mg plus panitumumab (5.6 months) and with sotorasib 240 mg plus panitumumab (3.9 months) compared with standard care (2.0 months).1, 48 Objective response rates were higher with combination therapy, particularly with the 960 mg sotorasib dose (26.4 versus 0% with standard care).48
The American Society of Clinical Oncology (ASCO) guideline on mCRC recommends the use of anti-EGFR therapy plus doublet chemotherapy as first-line therapy for microsatellite stable (MSS) or proficient mismatch repair (pMMR) left-sided RAS wild-type mCRC.12004 Doublet chemotherapy regimens include folinic acid/fluorouracil/oxaliplatin (FOLFOX) and folinic acid/fluorouracil/irinotecan (FOLFIRI).12004 Capecitabine plus oxaliplatin may be used as a substitute for folinic acid/fluorouracil/oxaliplatin.12004
Anti-EGFR therapy should not be used as first-line treatment in patients with right-sided, RAS wild-type mCRC.12004 These patients should instead receive chemotherapy combined with anti-VEGF therapy.12004
Anti-EGFR therapy is also not recommended for patients with RAS-mutant mCRC.12004 The use of anti-EGFR agents in combination with triplet chemotherapy is not recommended.12004 While anti-EGFR therapy is the preferred option, anti-VEGF therapy remains an effective alternative for treatment-naïve patients with left-sided, RAS wild-type mCRC in the first line setting.12004
Dispensing and Administration Precautions
Panitumumab is administered by IV infusion.1 The drug should not be administered by rapid IV injection, such as IV push or bolus. 1
Panitumumab is commercially available in single-dose vials at a concentration of 20 mg/mL.1
Panitumumab injection should be inspected visually for particulate matter and discoloration prior to administration.1 Solutions of the drug should be colorless but may contain a small amount of visible, translucent-to-white, amorphous, proteinaceous particulates; the solution should not be administered if discoloration or cloudiness is observed, or if foreign matter is present.1 The vials should not be shaken.1
Panitumumab vials should be protected from direct sunlight and stored at 2-8°C; freezing should be avoided.1
For IV infusion, the appropriate dose of panitumumab injection (containing 20 mg/mL) should be withdrawn into a syringe using a 21-gauge or larger gauge (smaller bore) hypodermic needle; do not use needle-free devices to withdraw vial contents.1 Dilute in 0.9% sodium chloride injection to a total volume of 100 mL using aseptic technique; doses exceeding 1 g should be diluted in 0.9% sodium chloride injection to a total volume of 150 mL.1 The final concentration should not exceed 10 mg/mL.1 The diluted solution should be mixed by gentle inversion and should not be mixed or diluted with other drugs or infusion solutions.1 Any unused portion left in the vial should be discarded since the injection contains no preservative.1
The diluted infusion solution may be stored at room temperature for up to 6 hours or at 2-8°C for up to 24 hours; freezing should be avoided.1
After dilution, panitumumab infusion solution should be administered IV through an appropriate 0.2- or 0.22-µm inline filter.1 Solutions of the drug should be administered using an infusion pump and infused through a peripheral IV line or indwelling IV catheter; the infusion line should be flushed with 0.9% sodium chloride injection before and after IV panitumumab administration.1 Doses of panitumumab of 1 g or less should be infused over 60 minutes; if tolerated, subsequent doses can be infused over 30 to 60 minutes.1 Doses exceeding 1 g should be infused over 90 minutes.1
RAS wild-type Metastatic Colorectal Cancer
For the treatment of adults with RAS wild-type mCRC as monotherapy or in combination with FOLFOX, the recommended dosage of panitumumab is 6 mg/kg administered as an IV infusion every 14 days until disease progression or unacceptable toxicity occurs.1
KRAS G12C-mutated Metastatic Colorectal Cancer
For the treatment of adults with KRAS G12C-mutated mCRC in combination with sotorasib, the recommended dosage of panitumumab is 6 mg/kg administered as an IV infusion every 14 days until disease progression, unacceptable toxicity occurs, or until sotorasib is withheld or discontinued.1 Administer the first sotorasib dose prior to the first panitumumab infusion.1
Dosage Modifications for Toxicity
In patients who develop mild or moderate (grade 1 or 2) infusion-related reactions, the infusion rate should be reduced by 50% for the duration of that infusion.1
In patients who develop severe (grade 3 or 4) infusion-related reactions, immediately stop the panitumumab infusion.1 Permanently discontinue panitumumab depending on the severity and/or persistence of the reaction.1
In patients with a first occurrence of grade 3 dermatologic toxicity, withhold 1-2 doses, and reinitiate at the original dosage if the reaction improves to grade 3 or lower.1 Permanently discontinue if no recovery occurs after withholding 1‒2 doses.1
In patients with a second occurrence of grade 3 dermatologic toxicity, withhold 1-2 doses, and reinitiate 80% of the original dosage if the reaction improves to grade 3 or lower.1 Permanently discontinue if no recovery occurs after withholding 1‒2 doses.1
In patients with a third occurrence of grade 3 dermatologic toxicity, withhold 1-2 doses, and reinitiate 60% of the original dosage if the reaction improves to grade 3 or lower.1 Permanently discontinue if no recovery occurs after withholding 1‒2 doses.1
In patients with a fourth occurrence of grade 3 dermatologic toxicity, or in patients with a grade 4 reaction, permanently discontinue panitumumab.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturers make no specific dosage recommendations for geriatric patients.1
Dermatologic and Soft Tissue Toxicity
A boxed warning about the risk of dermatologic toxicity is included in the prescribing information for panitumumab.1 In clinical trials, dermatologic toxicities occurred in 90% of patients and were grade 3 in 15% of patients receiving panitumumab monotherapy.1 Among patients who received panitumumab with the FOLFOX regimen, dermatologic toxicity occurred in 96% of patients, with grade 4 severity occurring in 1% and grade 3 in 32% of patients.1 Among patients who received panitumumab with sotorasib, dermatologic toxicity occurred in 94% of patients, with grade 3 severity reported in 16% of patients.1 Dermatologic toxicity manifested as dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and/or skin fissures.1 Life-threatening and fatal infectious complications (including necrotizing fasciitis, abscesses, and sepsis) and bullous mucocutaneous disease (including blisters, erosions, and skin sloughing) have been observed.1 If adverse dermatologic or soft tissue effects occur during therapy, monitor patients for possible inflammatory or infectious complications and initiate appropriate therapy.1 Withhold or discontinue therapy for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications.1
Other Warnings and Precautions
Increased Tumor Progression, Increased Mortality, or Lack of Benefit in Patients with RAS-Mutant mCRC Receiving Panitumumab Monotherapy or in Combination with Oxaliplatin-based Chemotherapy
Panitumumab monotherapy or in combination with oxaliplatin-based chemotherapy is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS.1 Exposure to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, including panitumumab and cetuximab, in patients with tumors containing RAS mutations resulted in adverse reactions without clinical benefit.1
In a trial comparing panitumumab plus FOLFOX to FOLFOX alone in patients with RAS-mutant metastatic colorectal cancer (mCRC) tumors, overall survival was shorter in patients who received the combination compared to FOLFOX alone.1
Electrolyte Depletion/Monitoring
Panitumumab can cause progressively decreasing serum magnesium levels leading to severe (grade 3 or 4) hypomagnesemia.1
In clinical trials, among patients who received panitumumab as monotherapy, decreased magnesium occurred in 38% of patients, including grade 4 (1.3%) and grade 3 (2.6%) cases.1 Among patients who received panitumumab in combination with FOLFOX, decreased magnesium occurred in 51% of patients, including grade 4 (5%) and grade 3 (6%) cases.1 In patients receiving panitumumab in combination with sotorasib across clinical studies, decreased magnesium occurred in 69% of patients, including grade 4 (2.4%) and grade 3 (14%) cases.1 Other electrolyte disturbances, including hypokalemia, have also been observed.1
Monitor patients for hypomagnesemia and hypocalcemia prior to initiating panitumumab treatment, periodically during treatment, and for up to 8 weeks after the completion of treatment.1 Replete magnesium and other electrolytes as appropriate.1
Infusion-related reactions occurred in 4% of patients, and severe reactions (grade 3 or 4) occurred in 1% of patients taking panitumumab in a monotherapy clinical trial.1
Infusions reactions manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur after panitumumab administration.1 Fatal infusion reactions occurred in postmarketing experience.1 Terminate the infusion for severe infusion reactions.1
Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with panitumumab.1
Among patients who received panitumumab as monotherapy, acute renal failure occurred in 2% of patients, including grade 3 or 4 (2%) cases.1 Among patients who received panitumumab in combination with FOLFOX, acute renal failure occurred in 2% of patients, including grade 3 or 4 (2%) cases.1 In patients receiving panitumumab in combination with sotorasib across clinical studies, acute renal failure occurred in 3.2% of patients, including grade 3 (0.8%) cases.1
Monitor patients for diarrhea and dehydration, provide supportive care (including anti-emetic or anti-diarrheal therapy) as needed and withhold panitumumab if necessary.1
Pulmonary Fibrosis/Interstitial Lung Disease
Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with panitumumab.1 Pulmonary fibrosis occurred in less than 1% of patients enrolled in clinical studies of panitumumab.1 Grade 1 ILD/pneumonitis occurred in 0.8% of patients enrolled in clinical studies of panitumumab in combination with sotorasib.1
In the event of acute onset or worsening of pulmonary symptoms, interrupt panitumumab therapy.1 Discontinue panitumumab therapy if ILD is confirmed.1 In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, consider the benefits of therapy with panitumumab versus the risk of pulmonary complications.1
Exposure to sunlight can exacerbate dermatologic toxicity.1 Advise patients to wear sunscreen and hats and limit sun exposure during therapy.1
Serious cases of keratitis, ulcerative keratitis, and corneal perforation have occurred with panitumumab use.1
Among patients who received panitumumab in combination with FOLFOX, keratitis occurred in 0.3% of patients.1 In patients receiving panitumumab in combination with sotorasib across clinical studies, keratitis occurred in 1.6% of patients, ulcerative keratitis occurred in 0.8%, and vernal keratoconjunctivitis in 0.8%; all reactions were grade 1-2.1
Monitor for evidence of keratitis, ulcerative keratitis, or corneal perforation.1 Interrupt or discontinue panitumumab therapy for acute or worsening keratitis, ulcerative keratitis, or corneal perforation.1
Increased Mortality and Toxicity with Panitumumab in Combination with Bevacizumab and Chemotherapy
In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of panitumumab to the combination of bevacizumab and chemotherapy resulted in decreased overall survival and increased incidence of grade 3-5 adverse reactions.1 Grade 3-4 adverse reactions occurring at a higher rate in panitumumab-treated patients included rash/acneiform dermatitis, diarrhea, dehydration, primarily occurring in patients with diarrhea, hypokalemia, stomatitis/mucositis, and hypomagnesemia.1
Grade 3-5 pulmonary embolism occurred at a higher rate in panitumumab-treated patients and included fatal events in <1% of panitumumab-treated patients.1
As a result of the toxicities experienced, patients randomized to panitumumab, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-fluorouracil, and/or infusional 5-fluorouracil) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.1
Fetal/Neonatal Morbidity and Mortality
Panitumumab can cause fetal harm based on animal data and the mechanism of action of the drug.1 Embryolethality has been demonstrated in animals.1 No studies have been conducted to date in pregnant women.1
Apprise pregnant women and females of reproductive potential of the potential hazard to the fetus.1 Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of panitumumab.1
As with all therapeutic proteins, there is a potential for immunogenicity with panitumumab.1 In clinical studies of 23-week treatment with panitumumab monotherapy, the incidence of anti-panitumumab antibodies was 5.2%.1 Of the patients who tested positive for anti-panitumumab antibodies, 18.9% had neutralizing antibodies against panitumumab.1
In clinical studies of 23-week treatment with panitumumab in combination with chemotherapy, the incidence of anti-panitumumab antibodies was 3.2%.1 Of the patients who tested positive for anti-panitumumab antibodies, 14.9% had neutralizing antibodies against panitumumab.1
There was no identified clinically important effect of anti-panitumumab-antibodies on panitumumab pharmacokinetics following monotherapy.1 The effect of anti-panitumumab antibodies on the pharmacokinetics, following combination therapy, and on the safety and effectiveness of panitumumab has not been fully characterized.1
Based on its mechanism of action and findings from animal studies, panitumumab may cause fetal harm when administered to pregnant women.1 Limited available data on the use of panitumumab in pregnant women are insufficient to inform a risk of adverse pregnancy-related outcomes.1
Panitumumab is a human immunogloblulin G (IgG) monoclonal antibody and may be transferred across the placenta during pregnancy.1
Reproduction studies in cynomolgus monkeys treated with 1.25-5 times the recommended human dosage of panitumumab resulted in significant embryolethality and abortions; however, no other evidence of teratogenesis was noted in offspring.1
Advise pregnant women of the potential risk to the fetus.1
There are no data on the presence of panitumumab in human milk or the effects of panitumumab on the breast-fed infant or on milk production.1 Human IgG is distributed into human milk.1 Published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts.1
Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in breast-feeding infants from panitumumab, advise women not to breast-feed during treatment with panitumumab and for 2 months after the last dose.1
Females and Males of Reproductive Potential
Panitumumab may cause fetal harm when administered to pregnant women.1 Advise females of reproductive potential to use effective contraception during treatment and for 2 months after the last dose of panitumumab.1
Panitumumab may reduce fertility in females of reproductive potential based on animal data; effects in animals were reversible.1
Safety and efficacy not established in pediatric patients.1
Among patients who received panitumumab monotherapy for recurrent or refractory mCRC, 36% of patients were 65 years of age and older while 8% were 75 years of age and older.1 No overall differences in safety or efficacy were observed in geriatric patients (≥65 years of age) treated with panitumumab monotherapy.1
Among patients who received panitumumab plus FOLFOX for wild-type KRAS-mutated mCRC, 40% of patients were 65 years of age and older while 8% were 75 years of age and older.1 Patients >65 years of age experienced an increased incidence of serious adverse events and an increased incidence of serious diarrhea as compared to younger patients.1
In a pooled analysis of patients who received panitumumab in combination with sotorasib for KRAS G12C-mutated mCRC, 30% of patients were 65 years of age and older while 9% were 75 years of age and older.1 No overall differences in safety or efficacy were observed in geriatric patients (≥65 years of age) compared to younger patients treated with panitumumab in combination with sotorasib.1
The manufacturer does not provide any specific information regarding panitumumab use in patients with hepatic impairment.1
No clinically important differences in panitumumab pharmacokinetics were observed in patients with mild or moderate hepatic impairment (total bilirubin ≤3 times the upper limit of normal and any AST).1
The manufacturer does not provide any specific information regarding panitumumab use in patients with renal impairment.1
No clinically important differences in panitumumab pharmacokinetics were observed in patients with mild or moderate renal impairment (creatinine clearance 30-89 mL/minute).1
The most common adverse reactions (≥20%) of panitumumab as monotherapy are skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.1
The most common adverse reactions (≥20%) in clinical trials of panitumumab in combination with FOLFOX chemotherapy are diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin.1
The most common adverse reactions (≥20%) in clinical trials of panitumumab in combination with sotorasib are rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain.1 The most common grade 3 or 4 laboratory abnormalities in 4.3% of patients were decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium.1
No formal drug interaction studies of panitumumab have been performed.1, 16
Increased toxicity (pulmonary embolism, dermatologic toxicity, diarrhea, dehydration, hypomagnesemia) may result during concurrent therapy with bevacizumab and panitumumab.1
Fluoropyrimidines (e.g., Fluorouracil)
Pharmacokinetic interaction is unlikely.8
Pharmacokinetic interaction is unlikely.8
Increased incidence and severity of chemotherapy-induced diarrhea reported following addition of panitumumab to irinotecan, direct IV injection (“bolus”) fluorouracil, and leucovorin (the IFL regimen) in a clinical study.1, 17
Pharmacokinetic interaction is unlikely.8 However, the manufacturer states that use of panitumumab in combination chemotherapy regimens is not approved.1
There is a potential pharmacologic interaction (increased risk of dermatological toxicity).42 Although experience with concurrent panitumumab and radiation therapy is limited to date, combined use of cetuximab (another EGFR inhibitor) and radiation therapy has been associated with an increased risk of high-grade radiation dermatitis, rash, and mucositis.42
Panitumumab, a recombinant human IgG2 kappa monoclonal antibody that specifically binds to the human epidermal growth factor receptor (EGFR, HER1, c-erbB-1), is an antineoplastic agent.1, 2, 3, 4, 5, 6, 7, 8, 31 The drug is an immunoglobulin containing a fully human framework.1, 2, 3, 5, 6, 7, 8, 31
Human epidermal growth factor receptor (EGFR, HER1, c-erbB-1) is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases, which includes EGFR (HER1, c-erbB-1), HER2/ neu , HER3, and HER4.1, 5, 7, 8 While EGFR is expressed in many normal epithelial tissues (e.g., skin, hair follicle), overexpression of the glycoprotein is detected in human carcinomas (e.g., colon, rectum).1, 2, 3, 5, 6 Interaction of EGFR with its normal ligands (e.g., EGF, transforming growth factor [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 and panitumumab).1, 33, 44
Panitumumab binds specifically and with high affinity to the extracellular domain of EGFR on both normal and tumor cells and competitively blocks the cellular action of EGF and other ligands (e.g., TGF-α).1, 2, 3, 5, 6, 7, 8, 31 In nonclinical studies, 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 In vitro tests and in vivo animal studies have demonstrated that panitumumab inhibits the growth and survival of selected human tumor cell lines that overexpress EGFR,1, 2, 5, 6, 31 while such antitumor effects were not observed in human cancer xenografts that lacked EGFR expression.5, 6
The pharmacokinetics of panitumumab 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.1 Following administration of the recommended regimen of panitumumab (6 mg/kg by IV infusion every 2 weeks), steady-state panitumumab concentrations are achieved by the third infusion.1, 2, 8, 31 The mean elimination half-life of panitumumab following multiple dosing is approximately 7.5 days.1, 2, 8, 31
No clinically important differences in the pharmacokinetics of panitumumab were observed based on age (21-88 years of age), sex, race (White, Black, and Asian), mild or moderate renal impairment (creatinine clearance 30-89 mL/minute), mild or moderate hepatic impairment (total bilirubin ≤3 times the upper limit of normal and any AST), and EGFR membrane-staining intensity (1+, 2+, and 3+) in tumor cells.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Amgen Inc. Vectibix® (panitumumab) injection for intravenous use prescribing information. Thousand Oaks, CA; 2025 Jun.
2. Hoy SM, Wagstaff AJ. Panitumumab in the treatment of metastatic colorectal cancer. Drugs . 2006; 66:2005-14; discussion 2015-6. [PubMed 17100412]
3. Gibson TB, Ranganathan A, Grothey A. Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clin Colorectal Cancer . 2006; 6:29-31. [PubMed 16796788]
4. Peeters M, Van Cutsem E, Siena S et al. A phase 3, multicenter, randomized controlled trial (RCT) of panitumumab plus best supportive care (BSC) vs BSC alone in patients (pts) with metastatic colorectal cancer (mCRC). Oral presentation at 97th Annual Meeting of the American Association for Cancer Research. Washington, DC: 2006 Apr 1-5.
5. Cohenuram M, Saif MW. Panitumumab the first fully human monoclonal antibody: from the bench to the clinic. Anti-cancer Drugs . 2007; 18:7-15. [PubMed 17159497]
6. Yang XD, Jia XC, Corvalan JR et al. Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol . 2001; 38:17-23. [PubMed 11255078]
7. Saif MW, Cohenuram M. Role of panitumumab in the management of metastatic colorectal cancer. Clin Colorectal Cancer . 2006; 6:118-24. [PubMed 16945167]
8. Wainberg Z, Hecht JR. Panitumumab in colon cancer: a review and summary of ongoing trials. Expert Opin Biol Ther . 2006; 6:1229-35. [PubMed 17049019]
13. Van Cutsem E, Peeters M, Siena S et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol . 2007; 25:1658-64. [PubMed 17470858]
16. Amgen Inc. Vecitibix Patient Site: Important Safety Information. Accessed March 31, 2026.
17. Berlin J, Posey J, Tchekmedyian S et al. Panitumumab with irinotecan/leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer. Clin Colorectal Cancer . 2007; 6:427-32. [PubMed 17531105]
31. Peeters M, Balfour J, Arnold D. Review article: panitumumab--a fully human anti-EGFR monoclonal antibody for treatment of metastatic colorectal cancer. Aliment Pharmacol Ther . 2008; 28:269-81. [PubMed 19086328]
33. Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol . 2008; 26:1626-34. [PubMed 18316791]
37. Giusti RM, Shastri K, Pilaro AM et al. U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Clin Cancer Res . 2008; 14:1296-302. [PubMed 18316547]
42. Tejwani A, Shenhong W, Jia Y et al. Increased risk of high-grade dermatologic toxicities with radiation plus epidermal growth factor receptor inhibitor therapy. Cancer . 2009; 115:1286-99. [PubMed 19170238]
44. Allegra CJ, Jessup JM, Somerfield MR et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol . 2009; 27:2091-6. [PubMed 19188670]
45. Price TJ, Peeters M, Kim TW, et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014;15(6):569-579.
46. Kim TW, Elme A, Kusic Z, et al. A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer. Br J Cancer. 2016;115(10):1206-1214.
47. Douillard JY, Siena S, Cassidy J, et al. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014;25(7):1346-1355.
48. Fakih MG, Salvatore L, Esaki T, et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023;389(23):2125-2139.
100. Institute of Safe Medicine Practices. ISMP List of High-Alert Medication in Acute Care Settings. Accessed Mar 31, 2026. [Web]
12004. Morris V, Kennedy E, Baxter N, et al. Treatment of metastatic colorectal cancer: ASCO guideline. J Clin Oncol. 2022;41:678-700.