Hubbry Logo
PanitumumabPanitumumabMain
Open search
Panitumumab
Community hub
Panitumumab
logo
7 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Panitumumab
Panitumumab
Panitumumab
View on Wikipedia
from Wikipedia
Panitumumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetEpidermal growth factor receptor (EGFR)
Clinical data
Trade namesVectibix
Other namesABX-EGF
AHFS/Drugs.comMonograph
MedlinePlusa607066
License data
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life~9.4 days (range: 4-11 days)
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
PDB ligand
Chemical and physical data
FormulaC6398H9878N1694O2016S48
Molar mass144324.12 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Panitumumab, sold under the brand name Vectibix, is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as EGF receptor, EGFR, ErbB-1 and HER1 in humans).[1][2]

Panitumumab is manufactured by Amgen and was originally developed by Abgenix Inc.

In 2014, Amgen and Illumina entered into an agreement to develop a companion diagnostic to accompany panitumumab.[3]

Medical uses

[edit]

Panitumumab was approved by the U.S. Food and Drug Administration (FDA) for the first time in September 2006, for "the treatment of EGFR-expressing metastatic colorectal cancer with disease progression" despite prior treatment.[4] Panitumumab was approved by the European Medicines Agency (EMEA) in 2007, and by Health Canada in 2008, for "the treatment of refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS".

Panitumumab was the first monoclonal antibody to demonstrate the use of KRAS as a predictive biomarker.

Contraindications

[edit]

Panitumumab does not work in patients who have KRAS or NRAS mutations.[5]

Adverse effects

[edit]

Panitumumab has been associated with skin rash, fatigue, nausea, diarrhea, fever, and decreased magnesium levels. Often, skin rash is noted in the sun exposed parts of the body, such as the face or chest. Oral antibiotics may be needed for worsening skin rash, such as one accompanied with blisters and ulcers. Otherwise, topical steroid creams like hydrocortisone may help.[6]

Ocular toxicity or keratitis was observed in 16% of patients on panitumumab, usually necessitating the discontinuance of therapy.[7]

In clinical trials, 90% of patients had dermatological toxicities and 15% of those were severe. Because of this, panitumumab has a boxed warning cautioning patients. Skin toxicities were typically apparent two weeks after beginning treatment. More severe skin toxicities were associated with improved progression free survival and overall survival.[7]

Pulmonary fibrosis and interstitial lung disease were observed in clinical trials.[7]

Pharmacology

[edit]

Mechanism of action

[edit]
Main article: Epidermal growth factor receptor

EGFR is a transmembrane protein. Panitumumab works by binding to the extracellular domain of the EGFR preventing its activation. This results in halting of the cascade of intracellular signals dependent on this receptor.[8]

Pharmacokinetics

[edit]

The pharmacokinetics (PK) of panitumumab shows the so-called target-mediated disposition behavior.[9] However, the pharmacokinetics is approximately linear at clinical doses, and the terminal half-life for a typical male patient of 80 kg and 60 years of age with colorectal cancer is about 9.4 days.[medical citation needed]

History

[edit]

Panitumumab was generated using Abgenix's XenoMouse platform technology, in which engineered mice were utilized to produce human antibodies. Abgenix partnered with Immunex Corporation to develop the antibody, and Amgen acquired Immunex in 2003. In 2006, Amgen acquired Abgenix as well. In 2013, Amgen formed an agreement with Zhejiang Beta Pharma to form Amgen Beta Pharmaceuticals and market panitumumab in China. Amgen and Takeda have an agreement under which Takeda will develop and commercialise panitumumab in Japan.[10] Panitumumab is licensed to Dr. Reddy's Laboratories[11] in India and GlaxoSmithKline in the UK.[citation needed]

FDA approval

[edit]

Panitumumab was initially approved on September 27, 2006, 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.[12] In July 2009, the FDA updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab and cetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations.[13] This was the result of a study, which demonstrated lack of benefit with Panitumumab in patients who carried NRAS mutations.[5]

It is also approved as a first-line agent in combination with FOLFOX.[7]

Research

[edit]

Panitumumab is being studied in numerous phase II and III clinical trials. Phase III clinical trials include treatment of esophageal cancer,[14] urothelial carcinoma,[15] metastatic head and neck cancer,[16] and liver metastasis in colorectal cancer.[17] Early trials showed limited efficacy in patients with malignant melanoma, bladder cancer, prostate cancer, and renal cell carcinoma.[10]

Panitumumab vs. cetuximab

[edit]

Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) 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).[18] It is not clear at this time, if one drug is superior to the other. In one of the studies, both these drugs were noted to be similar in activity.[19]

References

[edit]

Further reading

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Panitumumab

View on Grokipedia
from Grokipedia
Panitumumab is a recombinant, fully immunoglobulin G2 (IgG2) kappa that specifically binds to the (EGFR) on the surface of cells, inhibiting ligand-induced receptor autophosphorylation and downstream signaling pathways that promote tumor , survival, and . Developed by and marketed under the brand name Vectibix, it is administered intravenously and has a molecular weight of approximately 147 kDa, produced using Chinese hamster ovary cells. First approved by the U.S. (FDA) in September 2006 for the treatment of (EGFR)-expressing metastatic (mCRC) refractory to standard containing fluoropyrimidine, , and , its indications have since been refined based on tumor status. Panitumumab is indicated for the first-line treatment of RAS wild-type mCRC in combination with FOLFOX (folinic acid, fluorouracil, and oxaliplatin), or as monotherapy following disease progression after treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. It is not recommended for patients with RAS-mutant mCRC due to evidence of reduced efficacy and potential harm, including increased tumor progression and mortality when used as monotherapy or with certain chemotherapies. In January 2025, the FDA expanded its approval to include combination therapy with sotorasib for adult patients with KRAS G12C-mutated mCRC who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, marking a targeted option for a specific mutation subtype previously resistant to anti-EGFR therapies. The standard dosage is 6 mg/kg administered as an intravenous infusion every 14 days until disease progression or unacceptable toxicity, with infusion times of 60 minutes for doses up to 1000 mg or 90 minutes for higher doses. Pharmacokinetically, panitumumab exhibits nonlinear, target-mediated clearance with a of approximately 7.5 days at , achieved after the third infusion, and no dose adjustments are required based on age, , , or mild-to-moderate hepatic or renal impairment. Common adverse effects include dermatologic toxicities such as and dermatitis acneiform (affecting up to 90% of patients, with 15% severe), hypomagnesemia, , and infusion reactions, necessitating careful monitoring and dose modifications. Nonclinical studies indicate reversible impairment of female fertility in animal models but no carcinogenicity or mutagenicity, and it carries warnings for embryo-fetal toxicity, requiring contraception use during treatment and for two months afterward. Clinical trials have demonstrated improved and response rates in eligible mCRC patients, particularly when combined with in the first- or second-line settings, underscoring its role in precision for biomarker-selected populations.

Medical Uses

Indications

Panitumumab, marketed as Vectibix, is approved by the U.S. (FDA) for the treatment of adult patients with wild-type RAS metastatic (mCRC), defined as tumors without mutations in or NRAS exons 2, 3, or 4 as confirmed by an FDA-approved test. Specifically, it is indicated as first-line therapy in combination with for wild-type RAS mCRC, particularly showing efficacy in left-sided tumors based on clinical evidence from the PRIME study. Additionally, it is approved as monotherapy for wild-type RAS mCRC following disease progression after prior fluoropyrimidine-, -, and irinotecan-containing regimens. In the , the (EMA) approves panitumumab for adult patients with wild-type RAS mCRC, including first-line use in combination with or , second-line combination with after prior fluoropyrimidine-based (excluding irinotecan), and monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens. Patient selection requires testing to confirm wild-type RAS status, with guidelines emphasizing the use of validated assays to exclude that predict lack of response to EGFR inhibitors like panitumumab. In January 2025, the FDA granted approval for panitumumab in combination with for adult patients with KRAS G12C-mutated, chemorefractory mCRC, as determined by an FDA-approved test, following prior fluoropyrimidine-, -, and irinotecan-based ; this expands options for a subset of RAS-mutant cases previously ineligible for EGFR-targeted . Panitumumab is not indicated for RAS-mutant mCRC except in this specific KRAS G12C combination, nor for patients with unknown RAS status. Investigational uses of panitumumab have been explored in clinical trials for other cancers, such as head and neck , but it lacks regulatory approval beyond mCRC indications.

Dosage and Administration

Panitumumab is administered as an intravenous infusion at a recommended dose of 6 mg/kg body weight every 14 days for the treatment of RAS wild-type metastatic , either as monotherapy or in combination with regimens such as . In combination with for first-line therapy, panitumumab is typically given prior to administration. For G12C-mutated metastatic following prior , the same dose of panitumumab is used in combination with 960 mg orally once daily, with sotorasib administered before the initial panitumumab infusion and continued until disease progression or unacceptable toxicity. The initial infusion should be administered over 60 minutes for doses of 1000 mg or less, or over 90 minutes for doses exceeding 1000 mg, through a low-protein-binding 0.2 μm or 0.22 μm in-line filter. Subsequent infusions may be shortened to 30–60 minutes if the first infusion is tolerated, with the drug diluted in 100 mL of 0.9% for doses up to 1000 mg or 150 mL for higher doses. No is routinely required, though facilities for managing severe reactions should be available during administration. Dose adjustments are recommended for managing toxicities, particularly dermatologic reactions. For grade 3 skin toxicity, panitumumab should be withheld for 1 to 2 doses; upon improvement to grade 1 or less, treatment may resume at the original dose for the first occurrence, 80% of the original dose for the second, and 60% for the third, with permanent discontinuation required for a fourth occurrence or any grade 4 toxicity. In cases of mild or moderate reactions, the infusion rate should be reduced by 50%, while severe reactions necessitate immediate termination and consideration of permanent discontinuation. For the combination, panitumumab should be temporarily withheld if sotorasib is paused or permanently discontinued if sotorasib is stopped. Patients receiving panitumumab require regular monitoring for dermatologic reactions, with assessments at baseline and prior to each dose, as well as periodic evaluation of levels such as magnesium and calcium throughout treatment and for up to 8 weeks after discontinuation. Treatment continues until disease progression or unacceptable toxicity occurs.

Safety and Contraindications

Contraindications

Panitumumab is contraindicated in patients with a history of severe or life-threatening reactions to the active substance or to any of the excipients. It is also contraindicated in individuals with or , due to the risk of exacerbating these conditions. Additionally, the combination of panitumumab with oxaliplatin-containing chemotherapy regimens is contraindicated in patients with RAS-mutant metastatic (mCRC) or unknown RAS tumor status, as it offers no benefit and may increase . Relative contraindications include use in patients with RAS-mutant mCRC when administered as monotherapy or in combination with oxaliplatin-based , where panitumumab is not indicated due to lack of efficacy and potential harm. Note that for KRAS G12C-mutated mCRC, panitumumab is indicated in combination with following prior . Caution is advised in patients with severe cardiac disease or uncontrolled , particularly when panitumumab is combined with regimens that may elevate cardiovascular risks. Current guidance indicates panitumumab can cause fetal harm based on showing embryolethality and fetal abnormalities at doses approximating human exposure; use during is not recommended. Effective contraception is recommended for women of reproductive potential during treatment and for at least 2 months after the last dose. For , panitumumab is not recommended, and women should avoid during treatment and for 2 months thereafter due to the potential for serious adverse reactions in nursing infants. Patients with a known history of severe infusion reactions should avoid panitumumab, as severe reactions, including , have been reported and require immediate discontinuation. Caution is warranted in individuals with prior severe dermatologic reactions to other (EGFR) inhibitors, as they may be at higher risk for similar toxicities with panitumumab.

Adverse Effects

Panitumumab treatment is associated with a range of adverse effects, primarily due to its targeting of the (EGFR), with dermatologic toxicities being the most prevalent. In clinical trials, the overall incidence of any-grade adverse events was high, but severe (grade 3 or 4) events were manageable in most cases. Dermatologic effects are the most common adverse reactions, occurring in up to 90% of patients receiving panitumumab monotherapy, with severe (grade 3 or higher) toxicities in approximately 15%. These include (57%), pruritus (58%), (22%), skin fissures (20%), and (25%, with 2% grade 3-4). In the ASPECCT trial comparing panitumumab to , any-grade skin toxicity affected 89.7% of patients in the panitumumab arm, with grade 3-4 events in 13.6%. Management typically involves topical antibiotics and moisturizers to mitigate risk and discomfort from skin barrier disruption. In combination with sotorasib for KRAS G12C-mutated mCRC, dermatologic toxicities occurred in 94% of patients (16% grade 3), including (87%, 26% grade 3-4), dry (28%), and pruritus (17%). Gastrointestinal adverse effects include diarrhea, reported in 21% of monotherapy patients (2% grade 3-4) and up to 62% in combination with (18% grade 3-4); with , diarrhea affected 28% (6% grade 3-4). Hypomagnesemia occurs frequently, with all-grade incidence of 38% in monotherapy (4% grade 3-4), 30% in combination with (7% grade 3-4), and 76% with (24% grade 3-4), often persisting long-term with continued treatment. In the ASPECCT trial, grade 3-4 hypomagnesemia affected 7% of panitumumab-treated patients. Infusion-related reactions occur in about 3% of patients (less than 1% grade 3-4), manifesting as , fever, or chills, with being rare. In the ASPECCT trial, grade 3-4 infusion reactions were reported in 0.5% of the panitumumab group. Serious adverse effects are less common but include pulmonary toxicity such as or fibrosis (<1% incidence in monotherapy). Ocular issues, including , affect 10-20% of patients overall, with 16% experiencing any ocular toxicity in monotherapy (5% ). Keratitis has been reported in up to 1.6% of patients in combinations (e.g., with ), and ulcerative keratitis in 0.8%; monitoring and interruption are recommended for severe cases. Increased infection risk arises from dermatologic disruptions, with leading to severe complications in some cases. Long-term effects from pivotal trials like ASPECCT include nail changes (e.g., persisting beyond initial treatment) and , contributing to ongoing dermatologic and gastrointestinal management needs.

Panitumumab is a fully immunoglobulin G2 (IgG2) kappa that specifically targets the extracellular ligand-binding domain of the (EGFR, also known as HER1 or ErbB1) on both normal and tumor cells. By binding with high affinity (Kd ≈ 0.05 nM), panitumumab competitively inhibits the attachment of natural ligands such as (EGF) and transforming growth factor-alpha (TGF-α). This binding prevents receptor dimerization and subsequent autophosphorylation, thereby blocking the activation of intracellular tyrosine kinases associated with EGFR. The inhibition of EGFR activation disrupts downstream signaling pathways, including the RAS/RAF/MEK/ERK (MAPK) cascade and the PI3K/AKT pathway, which are critical for cell survival and proliferation. In EGFR-overexpressing tumor cells, this blockade leads to reduced cell proliferation, induction of apoptosis, decreased production of pro-inflammatory cytokines and vascular endothelial growth factor (VEGF), and inhibition of angiogenesis and metastasis. Additionally, panitumumab promotes the internalization and degradation of EGFR, further limiting its signaling capacity. Due to its IgG2 subclass, panitumumab exhibits minimal (ADCC), as the Fc region has low affinity for Fcγ receptors on immune effector cells like natural killer cells. Its therapeutic efficacy is particularly relevant in , where it is effective primarily in tumors with wild-type RAS ( and NRAS) for monotherapy or standard combinations, as activating RAS mutations enable signaling bypass independent of EGFR inhibition. However, as of January 2025, it is also approved in combination with for G12C-mutated metastatic following prior ; in this setting, EGFR activation serves as a resistance mechanism to G12C inhibition, and panitumumab blocks this bypass pathway to enhance antitumor activity, as shown in preclinical models.

Pharmacokinetics

Panitumumab is administered via intravenous , typically over 60 minutes every two weeks, with near-complete of approximately 100% due to direct systemic delivery and the absence of an oral . The are nonlinear, with the area under the curve (AUC) increasing greater than dose-proportionally at doses below 2 mg/kg and becoming approximately dose-proportional at higher doses, reflecting saturable elimination pathways. Steady-state concentrations are achieved after approximately three to four s, supporting sustained (EGFR) binding essential for its therapeutic efficacy. Following administration, panitumumab distributes primarily within the vascular and spaces, with a central volume of distribution of approximately 3.95 L (or about 3.6 L/m²), consistent with its large molecular weight as a . It binds to EGFR expressed on tumor cells as well as normal tissues such as and gastrointestinal mucosa, influencing its tissue localization. Metabolism occurs through proteolytic degradation into small peptides and amino acids via the and receptor-mediated internalization, without involvement of hepatic enzymes. Elimination follows a two-compartment model with both linear clearance (via the ) and nonlinear, saturable clearance (EGFR-dependent), resulting in a mean clearance of 4.9 ± 1.4 mL/kg/day at that decreases with higher doses. The terminal is approximately 7.5 days, with a range of 3.6 to 10.9 days, allowing for biweekly dosing. In special populations, pharmacokinetics remain largely unchanged; no significant differences are observed in patients with mild to moderate renal impairment (creatinine clearance 30–89 mL/min) or hepatic impairment (total ≤3 × upper limit of normal), nor with variations in age (21–88 years), gender, or race. Body weight positively correlates with exposure, but dose adjustments are not required. Drug interactions are minimal, with no clinically significant effects on the of co-administered chemotherapies such as , , or ; however, concomitant use with other biologics warrants monitoring for potential that could indirectly affect exposure.

Development and History

Discovery and Early Development

Panitumumab, originally designated as ABX-EGF, was developed by Abgenix Inc. in the late 1990s using the company's proprietary XenoMouse technology, which involves transgenic mice engineered to produce fully human monoclonal antibodies by inactivating endogenous immunoglobulin loci and introducing human immunoglobulin transgenes. Abgenix was acquired by Amgen in April 2003, after which Amgen continued the development of panitumumab. This approach enabled the generation of high-affinity antibodies without murine components, reducing the risk of immunogenicity associated with earlier chimeric or humanized antibodies. The specific anti-epidermal growth factor receptor (EGFR) antibody, an IgG2 isotype, was identified through immunization of these mice with recombinant human EGFR extracellular domain, yielding panitumumab as a candidate with subnanomolar binding affinity (Kd ≈ 5 × 10^{-11} M). Preclinical studies demonstrated panitumumab's potent EGFR inhibition in , where it blocked binding (e.g., EGF and TGF-α) to the receptor's extracellular domain, preventing downstream signaling via receptor dimerization and autophosphorylation. , the induced significant tumor regression or growth inhibition in xenograft models, including those derived from colorectal and head and neck cancers, with complete tumor eradication observed in some EGFR-overexpressing lines at doses of 0.1–1 mg/kg administered weekly. These effects were attributed to blockade of EGFR-mediated proliferation and , with enhanced efficacy in models exhibiting high EGFR expression levels. The rationale for targeting EGFR stemmed from its overexpression in approximately 60–80% of colorectal cancers, where it drives oncogenesis through hyperactivation of pathways like PI3K/AKT and MAPK, and panitumumab's fully structure offered advantages over chimeric antibodies such as by minimizing anti-drug responses and infusion reactions. Early development milestones included the initiation of phase I clinical trials in July 1999, focusing on safety, , and preliminary antitumor activity in patients with advanced solid tumors expressing EGFR, such as colorectal and prostate cancers. These trials established tolerability at doses up to 2.5 mg/kg biweekly, with no maximum tolerated dose identified and low observed. Intellectual property protection was secured through key filed between 1999 and 2005, including U.S. Patent No. 6,235,883 (filed May 5, 1999) covering the antibody sequence and methods for producing fully human anti-EGFR antibodies via XenoMouse technology, as well as subsequent filings on production processes and formulations.

Regulatory Approvals

Panitumumab, marketed as Vectibix, received its initial approval from the U.S. (FDA) on September 27, 2006, as a monotherapy for the treatment of (EGFR)-expressing metastatic (mCRC) refractory to standard regimens containing fluoropyrimidine, , and . This accelerated approval was supported by data from a pivotal phase III randomized trial demonstrating improved compared to best supportive care, and the initial label included a black box warning for severe dermatologic toxicity. The FDA expanded the indication on May 23, 2014, approving panitumumab in combination with (fluorouracil, leucovorin, and ) chemotherapy as first-line treatment for patients with wild-type mCRC. This update followed demonstration of superior in the PRIME trial for patients with wild-type tumors. The PRIME trial initially enrolled an unselected population and was powered for progression-free survival in the intent-to-treat population, but the protocol was amended to prospectively ascertain KRAS exon 2 status, with the primary efficacy analysis prespecified in the wild-type KRAS subgroup, showing benefit in wild-type and detriment in mutant tumors, supporting the initial restriction to KRAS wild-type patients. Subsequent label revisions in 2017 extended to full wild-type RAS (KRAS and NRAS exons 2-4) mCRC, based on retrospective post-hoc testing of additional RAS exons beyond KRAS exon 2 in the PRIME trial, which identified lack of benefit in those with other RAS mutations. More recently, on January 16, 2025, the FDA approved the combination of panitumumab with for adult patients with chemorefractory G12C-mutated mCRC, based on the phase III CodeBreaK 300 trial showing improved objective response rates and . In the , the (EMA) granted conditional marketing authorization for panitumumab on December 3, 2007, for the treatment of adult patients with non-resectable EGFR-expressing mCRC that is refractory to standard therapies including fluoropyrimidine-, -, and -containing regimens. This authorization was converted to full marketing authorization on January 15, 2015, with subsequent updates in 2011 and 2015 approving its use in combination with (, leucovorin, and ) or as first-line therapy for wild-type RAS mCRC, alongside requirements for RAS testing prior to initiation. Approvals in other regions followed closely: Health Canada authorized panitumumab on April 3, 2008, for refractory EGFR-expressing mCRC, aligning with initial U.S. and EU indications. In Japan, the Ministry of Health, Labour and Welfare approved it on April 16, 2010, for unresectable advanced or recurrent wild-type KRAS colorectal cancer refractory to standard chemotherapy. Label updates across these regions from 2013 to 2014 mandated RAS mutation testing to confirm wild-type status before treatment, reflecting evolving evidence on biomarker-driven efficacy. Prior to initial approval, programs provided panitumumab to eligible patients with mCRC through compassionate use protocols managed by the manufacturer.

Research and Clinical Investigations

Pivotal Trials

The Panitumumab Advanced Evaluation (PACCE) trial was a randomized phase IIIB study conducted from 2005 to 2009 that evaluated the addition of panitumumab to and either oxaliplatin- or irinotecan-based as first-line treatment for metastatic (mCRC). The trial enrolled 1,043 patients and was prematurely discontinued after an revealed decreased (PFS) in the panitumumab arm (median 8.8 months vs. 10.5 months with plus alone; hazard ratio [HR] 1.27, 95% [CI] 1.06-1.52) and increased grade 3/4 adverse events, particularly in the oxaliplatin cohort. These findings led to U.S. (FDA) label restrictions contraindicating the combination of panitumumab with , highlighting the risks of dual inhibition of (EGFR) and () pathways. The ASPECCT trial, a phase III non-inferiority study from 2010 to 2014, compared panitumumab monotherapy (6 mg/kg every 2 weeks) with (400 mg/m² initial dose followed by 250 mg/m² weekly) plus best supportive care in 999 patients with chemorefractory exon 2 wild-type mCRC. Panitumumab demonstrated non-inferior overall survival (OS) compared to (median 10.0 months vs. 9.6 months; HR 0.83, 95% CI 0.73-0.95), meeting the primary endpoint of retaining at least 50% of 's effect versus best supportive care. PFS was similar between arms (median 4.1 months vs. 4.4 months; HR 1.08, 95% CI 0.95-1.23), with comparable objective response rates (approximately 20%) but a more favorable safety profile for panitumumab, including lower rates of severe skin toxicity and hypomagnesemia. These results supported panitumumab's role as a standard option in refractory wild-type mCRC. The PRIME trial, a phase III study from 2006 to 2013, initially enrolled an unselected population of 1,183 patients with untreated mCRC and was powered for progression-free survival (PFS) in the intent-to-treat (ITT) population. The protocol was amended prior to efficacy analyses to prospectively ascertain KRAS exon 2 status, with the primary efficacy analysis prespecified in the wild-type (WT) KRAS subgroup, demonstrating significant PFS benefit in WT KRAS tumors (median 9.6 months vs. 8.0 months; HR 0.80, 95% CI 0.66-0.97; P=0.02) and detriment in mutant (MT) KRAS tumors (median 7.3 months vs. 8.8 months; HR 1.29, 95% CI 1.04-1.62; P=0.02). This supported the initial restriction of panitumumab labeling to KRAS WT mCRC. Subsequent retrospective post-hoc testing of additional RAS exons (KRAS exons 3 and 4, NRAS exons 2, 3, and 4) identified lack of benefit in patients with other RAS mutations, leading to further restriction to full RAS wild-type populations. The trial assessed panitumumab (6 mg/kg every 2 weeks) plus FOLFOX4 versus FOLFOX4 alone as first-line therapy, with extended biomarker analysis. In the RAS wild-type subgroup (n=512), panitumumab-FOLFOX4 significantly improved PFS (median 10.1 months vs. 7.9 months; HR 0.72, 95% CI 0.58-0.90; P=0.004) and OS (median 26.0 months vs. 20.2 months; HR 0.78, 95% CI 0.64-0.95; P=0.01) compared to FOLFOX4 alone. Objective response rates were higher with panitumumab (58% vs. 48%), though grade 3/4 skin rash occurred in 18% of the combination arm. These outcomes established panitumumab's efficacy in combination with oxaliplatin-based chemotherapy for RAS wild-type mCRC, influencing expanded labeling. The PEAK trial, a phase II randomized study from 2009 to 2015, compared panitumumab plus mFOLFOX6 versus plus mFOLFOX6 as first-line treatment in 170 patients with exon 2 wild-type mCRC, later analyzed for extended RAS status. In the RAS wild-type cohort (n=142), panitumumab improved PFS ( 13.0 months vs. 9.8 months; HR 0.65, 95% CI 0.44-0.96; P=0.029), particularly in left-sided tumors, and showed a trend toward better OS ( 36.9 months vs. 28.9 months; HR 0.76, 95% CI 0.53-1.11; P=0.15). Response rates favored panitumumab (58% vs. 39%), with no new safety signals beyond known EGFR inhibitor effects. The trial underscored panitumumab's potential superiority over in biomarker-selected populations. The CodeBreaK 300 trial, a phase III study completed by 2025, evaluated (960 mg daily) plus panitumumab (6 mg/kg every 2 weeks) versus investigator's choice of therapy (trifluridine-tipiracil or ) in 160 patients with previously treated G12C-mutated mCRC. The combination significantly prolonged PFS (median 5.6 months vs. 2.2 months; HR 0.49, 95% CI 0.34-0.69; P<0.0001), with objective response rates of 30% versus 1.9%, supporting FDA approval in January 2025 for this indication. OS showed a non-significant trend favoring the combination (median not reached vs. 12.3 months; HR 0.84, 95% CI 0.52-1.35), as the trial was not powered for this endpoint. Adverse events were manageable, with grade 3/4 and in 21% and 15% of the experimental arm, respectively.

Ongoing and Emerging Research

Recent research on panitumumab has focused on expanding its role in metastatic (mCRC) through novel combinations and optimized regimens, particularly following the 2025 approval of in combination with panitumumab for KRAS G12C-mutated cases. Extensions of the CodeBreaK 200 and 300 trials have investigated this pairing post-approval, demonstrating sustained efficacy in previously treated patients with maintained health-related (HRQoL). Specifically, data from a randomized trial published in The Lancet Oncology in August 2025 reported no significant deterioration in global HRQoL scores with plus panitumumab compared to standard , highlighting the regimen's tolerability in KRAS G12C-mutated mCRC. In maintenance therapy settings, studies have explored less toxic alternatives to traditional . A February 2025 study in Oncotarget evaluated low-dose combined with panitumumab in RAS wild-type mCRC patients after induction therapy, showing comparable to full-dose regimens but with reduced grade 3/4 toxicities, such as and . This approach aims to balance efficacy with improved patient tolerability during prolonged treatment. The OPTIPRIME phase II trial, presented at ESMO 2025, assessed a "stop-and-go" strategy of plus panitumumab followed by panitumumab in RAS/BRAF wild-type mCRC, achieving an objective response rate (ORR) of 74.8% during induction and an 83.5% rate of patients entering . This intermittent dosing design seeks to minimize cumulative while preserving antitumor activity. At ASCO 2025, preliminary from a phase II trial in liver-limited, unresectable RAS/BRAF wild-type mCRC showed no significant improvement in overall survival with upfront intensified panitumumab plus ( or mFOLFOX6) compared to mFOLFOX6 plus panitumumab, highlighting the need for refined patient selection. Retreatment strategies represent another active area, with the PARERE phase II trial (reported June 2025) comparing panitumumab rechallenge followed by versus the reverse sequence in chemorefractory RAS/BRAF wild-type mCRC guided by (ctDNA). The panitumumab-first arm showed superior ORR and , supporting ctDNA-informed sequencing to overcome prior resistance. Emerging investigations are also probing panitumumab's utility beyond approved colorectal indications, including non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), despite limited regulatory support. Ongoing trials, such as ComboMATCH arms, evaluate panitumumab in EGFR-overexpressing advanced solid tumors, including NSCLC subsets, while phase II studies in HNSCC combine it with or radiation to enhance response rates in recurrent disease. Challenges in panitumumab research persist, particularly around resistance mechanisms like acquired RAS mutations, which emerge in up to 20-30% of responders and drive MAPK pathway reactivation. Biomarker refinements beyond initial RAS testing, such as ctDNA monitoring for negative hyperselection of additional alterations (e.g., EGFR extracellular domain mutations or MET amplifications), are being integrated to predict and mitigate resistance, as evidenced by 2025 updates in precision oncology guidelines.

Comparisons with Similar Agents

Panitumumab versus Cetuximab

Panitumumab and are both monoclonal targeting the (EGFR), but they differ in their molecular structures. Panitumumab is a fully immunoglobulin G2 (IgG2) , which contributes to its low profile, with binding anti-panitumumab antibodies detected in less than 1% of patients treated with monotherapy. In contrast, is a chimeric immunoglobulin G1 (IgG1) , leading to higher , with non-neutralizing anti- antibodies observed in approximately 5% of patients. These structural differences result in panitumumab eliciting fewer immune responses overall compared to . In terms of efficacy for treating metastatic (mCRC), panitumumab and demonstrate comparable outcomes in patients with wild-type exon 2 tumors, as shown in the head-to-head ASPECCT phase 3 trial. The trial reported overall survival (OS) of 10.4 months with panitumumab versus 10.0 months with ( [HR] 0.97, 95% CI 0.84–1.11), establishing non-inferiority for panitumumab. (PFS) was also similar, at a of 4.1 months for panitumumab versus 4.4 months for (HR 1.00, 95% CI 0.88–1.14). Both agents are ineffective in patients with RAS-mutated tumors, where they provide no significant survival benefit, limiting their use to RAS wild-type cases per clinical guidelines. Safety profiles differ notably, particularly regarding infusion reactions and skin toxicities. Due to its fully human sequence, panitumumab is associated with lower rates of severe reactions compared to ; in the ASPECCT , grade 3–4 reactions occurred in fewer than 0.5% of panitumumab-treated patients versus 2% with . Skin toxicities, a common class effect of EGFR inhibitors, are comparable in incidence but vary in severity: grade 3–4 skin and disorders affected 13% of patients on panitumumab versus 10% on in the same , though some analyses indicate may lead to more severe events in certain subgroups. Administration schedules provide panitumumab with a advantage. Panitumumab is dosed at 6 mg/kg intravenously every 2 weeks, allowing for biweekly infusions that reduce clinic visits. , however, follows a weekly regimen: an initial of 400 mg/m² over 120 minutes, followed by 250 mg/m² over 60 minutes thereafter. This biweekly option for panitumumab is preferred in some guidelines for improving convenience without compromising . Regarding cost and access, panitumumab and have similar pricing structures, with per-patient costs influenced by dosing frequency; economic analyses often favor panitumumab due to fewer administrations, projecting savings of approximately $9,000–$23,000 per patient in chemorefractory settings. Both agents are widely accessible through standard pathways, though panitumumab's scheduling may enhance real-world utilization in resource-limited settings.

Panitumumab in Combination Therapies

Panitumumab has demonstrated enhanced efficacy when combined with chemotherapy regimens such as and in patients with RAS wild-type metastatic colorectal cancer (mCRC). In the PRIME , the addition of panitumumab to FOLFOX4 as first-line therapy significantly improved (PFS) from 7.9 months to 10.1 months and overall survival (OS) from 20.2 months to 26.0 months in patients without RAS mutations, with a higher objective response rate (ORR) of approximately 62% compared to 55% for FOLFOX4 alone. Similarly, the PEAK showed that panitumumab plus mFOLFOX6 improved OS to 36.9 months versus 28.9 months with plus mFOLFOX6 in RAS wild-type patients, establishing superior long-term outcomes for this combination in first-line treatment. These synergies arise from panitumumab's EGFR inhibition complementing the cytotoxic effects of - or irinotecan-based chemotherapy, leading to deeper tumor responses in biomarker-selected populations. In patients with KRAS G12C-mutated mCRC, panitumumab has been effectively paired with G12C inhibitors to overcome resistance in chemorefractory settings. The combination of and panitumumab received FDA approval in January 2025 for adult patients with previously treated G12C-mutated mCRC, based on the phase 3 CodeBreaK 300 trial, which reported a median PFS of 5.6 months for the duo versus 2.0 months for investigator's choice of therapy, with an ORR of 26% versus 0%. This regimen leverages panitumumab's blockade of adaptive EGFR signaling to enhance the covalent inhibition of G12C by , yielding meaningful clinical benefits in this molecular subset. Ongoing trials with , another G12C inhibitor, have shown PFS improvements of 6.9 months when combined with EGFR inhibitors such as ; similar combinations with panitumumab are under investigation for previously treated advanced G12C-mutated . Combinations with anti-angiogenic agents present mixed results, highlighting key limitations in toxicity profiles. The PACCE trial demonstrated that adding panitumumab to plus chemotherapy ( or ) in first-line mCRC increased severe adverse events, including grade 3/4 and , without improving PFS or OS, leading to recommendations against this triplet approach due to heightened without efficacy gains. In contrast, potential synergies with , a VEGFR2 inhibitor, are being explored in later-line settings for refractory mCRC, where sequential or combined use may offer vascular disruption complementary to EGFR targeting, though dedicated trials are needed to confirm benefits. Emerging strategies incorporate panitumumab into maintenance and retreatment regimens to optimize tolerability and sequencing. The 2025 PARERE trial, a phase 2 randomized study, evaluated panitumumab retreatment followed by versus the reverse sequence in chemorefractory RAS/BRAF wild-type mCRC guided by ctDNA, showing superior first-line ORR (16% vs. 2%) and PFS (4.2 months vs. 2.4 months) for the panitumumab-first approach, supporting its role in re-sensitizing tumors post-prior exposure. Additionally, low-intensity maintenance with panitumumab plus metronomic low-dose has shown promise in RAS wild-type mCRC, achieving median PFS of 8.5 months while reducing oxaliplatin-induced neuropathy through , offering a less toxic option after induction therapy. Despite these advances, panitumumab combinations exhibit clear limitations in specific subgroups and management. No benefits are observed in RAS-mutated or right-sided tumors, as retrospective analyses from PRIME and PEAK confirmed inferior PFS and OS in these cohorts compared to left-sided RAS wild-type cases. Triplet regimens, particularly with , are associated with increased gastrointestinal , such as severe and mucosal , necessitating careful patient selection and monitoring. These factors underscore the importance of testing and side-specific considerations to maximize .

References

  1. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125147s213lbl.pdf
  2. https://pmc.ncbi.nlm.nih.gov/articles/PMC8013163/
  3. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer
  4. https://pubmed.ncbi.nlm.nih.gov/34152568/
  5. https://pubmed.ncbi.nlm.nih.gov/20481659/
  6. https://pmc.ncbi.nlm.nih.gov/articles/PMC3871277/
  7. https://www.ema.europa.eu/en/documents/product-information/vectibix-epar-product-information_en.pdf
  8. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/214665Orig1s009correctedlbl.pdf
  9. https://www.pi.amgen.com/united_states/vectibix/vectibix_pi.pdf
  10. https://pubmed.ncbi.nlm.nih.gov/24739896/
  11. https://pmc.ncbi.nlm.nih.gov/articles/PMC3445939/
  12. https://www.ema.europa.eu/en/documents/procedural-steps-after/vectibix-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf
  13. https://go.drugbank.com/drugs/DB01269
  14. https://pmc.ncbi.nlm.nih.gov/articles/PMC2721355/
  15. https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.00849/full
  16. https://link.springer.com/article/10.1007/s40262-017-0590-9
  17. https://www.ema.europa.eu/en/documents/scientific-discussion/vectibix-epar-scientific-discussion_en.pdf
  18. https://pubmed.ncbi.nlm.nih.gov/11255078/
  19. https://link.springer.com/chapter/10.1385/1-59259-893-5:647
  20. https://aacrjournals.org/clincancerres/article/13/16/4664/12943/Panitumumab-a-Monoclonal-Anti-Epidermal-Growth
  21. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04621-6
  22. https://pmc.ncbi.nlm.nih.gov/articles/PMC3231982/
  23. https://www.sec.gov/Archives/edgar/vprr/0402/04028143.pdf
  24. https://patents.google.com/patent/US6235883B1/en
  25. https://pubmed.ncbi.nlm.nih.gov/17522246/
  26. https://investors.amgen.com/news-releases/news-release-details/fda-approves-first-line-use-vectibixr-panitumumab-plus-folfox
  27. https://www.nejm.org/doi/full/10.1056/NEJMoa1305275
  28. https://www.ema.europa.eu/en/medicines/human/EPAR/vectibix
  29. https://hemonc.org/wiki/Panitumumab_%28Vectibix%29
  30. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125147s0000_MedR.pdf
  31. https://clinicaltrials.gov/study/NCT00115765
  32. https://pubmed.ncbi.nlm.nih.gov/19114685/
  33. https://www.nejm.org/doi/full/10.1056/NEJMoa0808268
  34. https://clinicaltrials.gov/study/NCT01001377
  35. https://ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.3586
  36. https://pubmed.ncbi.nlm.nih.gov/24718886/
  37. https://clinicaltrials.gov/study/NCT00819780
  38. https://pubmed.ncbi.nlm.nih.gov/28424871/
  39. https://ascopubs.org/doi/10.1200/JCO.2013.53.2473
  40. https://clinicaltrials.gov/study/NCT05198934
  41. https://ascopubs.org/doi/10.1200/JCO-24-02026
  42. https://www.nejm.org/doi/full/10.1056/NEJMoa2308795
  43. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2825%2900352-3/fulltext
  44. https://www.oncotarget.com/news/pr/new-study-suggests-panitumumab-with-low-dose-capecitabine-as-a-safer-effective-maintenance-treatment-for-advanced-colorectal-cancer/
  45. https://oncodaily.com/oncolibrary/optiprime-trial-for-mcrc-at-esmo2025
  46. https://www.onclive.com/view/efficacy-of-upfront-panitumumab-plus-intensified-chemo-falls-short-in-liver-limited-unresectable-mcrc
  47. https://www.annalsofoncology.org/article/S0923-7534%2825%2904934-8/fulltext
  48. https://ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA3515
  49. https://www.cancer.gov/research/participate/clinical-trials/intervention/panitumumab?pn=1
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC12460141/
  51. https://ascopubs.org/doi/10.1200/JCO.22.01423
  52. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1398419/full
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC11900077/
  54. https://pmc.ncbi.nlm.nih.gov/articles/PMC5856878/
  55. https://pmc.ncbi.nlm.nih.gov/articles/PMC9249215/
  56. https://pubmed.ncbi.nlm.nih.gov/31616627/
  57. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70118-4/fulltext
  58. https://.ncbi.nlm.nih.gov/24739896/
  59. https://karger.com/ocl/article/94/4/191/239128/Different-Toxicity-of-Cetuximab-and-Panitumumab-in
  60. https://pmc.ncbi.nlm.nih.gov/articles/PMC2993438/
  61. https://www.sciencedirect.com/science/article/pii/S0149291816301606
  62. https://pubmed.ncbi.nlm.nih.gov/27085587/
  63. https://pmc.ncbi.nlm.nih.gov/articles/PMC5522523/
  64. https://aacrjournals.org/cancerdiscovery/article/14/6/982/745540/Efficacy-and-Safety-of-Adagrasib-plus-Cetuximab-in
  65. https://pmc.ncbi.nlm.nih.gov/articles/PMC2792961/
  66. https://journals.sagepub.com/doi/10.1177/1758834016635888
  67. https://www.annalsofoncology.org/article/S0923-7534(25)04934-8/fulltext
  68. https://pmc.ncbi.nlm.nih.gov/articles/PMC11823472/
  69. https://www.nature.com/articles/s41416-018-0165-z
Add your contribution
Related Hubs
User Avatar
No comments yet.