Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR, ErbB-1 and HER1 in humans).
Panitumumab is indicated for the treatment of patients with wild-type in both KRAS and NRAS, for metastatic colorectal cancer. (mCRC).
Panitumumab does not work in patients who have KRAS or NRAS mutations.
It is an IgG2 human monoclonal antibody.
It works by binding to the extracellular domain of the EGFR preventing its activation.
This binding results in halting of the cascade of intracellular signals dependent on this receptor.
Marketed as Vectibix.
Approved for the treatment of EGFR-expressing metastatic colorectal cancer with disease progression, despite prior treatment.
Panitumumab was the first monoclonal antibody to demonstrate the use of KRAS as a predictive biomarker.
Initially approved for EGFR-expressing, metastatic CRC with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens, based on the results of a study which showed clinical benefit in metastatic colorectal cancer patients.
The treatment of metastatic colorectal cancer must include information about KRAS mutations, as there is a lack of benefit with Panitumumab in patients who carried NRAS mutations.
It is also approved as a first-line agent in combination with FOLFOX.
Approved for the treatment of EGFR-expressing metastatic colorectal cancer with disease progression, despite prior treatment.
It is a treatment for refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS
Panitumumab demonstrates the use of KRAS as a predictive biomarker.
There is a lack of benefit with Panitumumab in patients who carry NRAS mutations.
Elimination half-life∼9.4 days (range: 4-11 days).
Side effects: skin rash, fatigue, nausea, diarrhea, fever, and decreased magnesium levels.
The skin rash is often noted in the sun exposed parts of the body.
Topical steroid creams like hydrocortisone may help with skin lesions.
Skin rash is primarily noted in the sun exposed parts of the body, such as the face or chest.
Oral antibiotics and topical steroid creams like hydrocortisone may help.
In clinical trials, 90% of patients had dermatological toxicities and 15% of those were severe.
Skin toxicities are apparent two weeks after beginning treatment.
Severe skin toxicities are associated with improved progression free survival and overall survival.
Ocular toxicity or keratitis occurs in 16% of patients on panitumumab, and
90% of patients have dermatological toxicities and 15% are severe.
Pulmonary fibrosis and interstitial lung disease were observed in clinical trials.
Contraindications include KRAS or NRAS mutations.
Panitumumab (IgG2) and cetuximab(IgG1) target EGFR , bunt
differ in their isotype and they might differ in their mechanism of action.
Monoclonal antibodies of the IgG1 isotype may activate the complement pathway and mediate antibody-dependent cellular cytotoxicity (ADCC).
Both these drugs were noted to be similar in activity.
Skin manifestations include: acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.
Fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing have been reported.
The drug 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.
Anti-EGFR antibodies in patients with tumors containing RAS mutations results in adverse reactions without clinical benefit from these agents.
Overall survival in patients with mutated RAS colorectal tumors treated with chemotherapy and pantimumab was shorter, than chemotherapy alone.
Progressively lowering of serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% of patients in clinical trials.
Hypokalemia, has also been observed.
4% of patients experience infusion reactions and 1% of patients severe infusion reactions.
Severe diarrhea and dehydration, leading to acute renal failure has been observed in treated patients.
Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed.
Exposure to sunlight can exacerbate dermatologic toxicity.
Corneal perforation, from keratitis and ulcerative colitis have been reported.
In 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 OS and increased incidence of grade 3-5 adverse reactions. 3-4 adverse reactions
Grade 3-5 pulmonary embolism occurred at a higher rate in panitumumab treated patients and included fatal events.
Patients randomized to panitumumab. bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.
It can cause fetal harm when administered to a pregnant woman.
With monotherapy, the most commonly reported adverse reactions: skin rash, paronychia, fatigue, nausea, and diarrhea.
The most commonly reported adverse reactions with Panitumumab plus FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin.
Panitumumab (IgG2) and cetuximab (IgG1) both target EGFR, but differ in their isotype and they might differ in their mechanism of action.