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Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.

PANitumumab

( PAN-i-TOOM-ue-mab )
Funding:
New Drug Funding Program
  • Panitumumab - Metastatic Colorectal Small Bowel or Appendiceal Cancer
  • Panitumumab - In Combination with Chemotherapy for First Line Metastatic Colorectal Small Bowel or Appendiceal Cancer
Other Name(s): Vectibix®
Appearance: Colorless solution mixed into larger bags of fluids
A - Drug Name

PANitumumab

COMMON TRADE NAME(S):   Vectibix®

 
B - Mechanism of Action and Pharmacokinetics

 

Panitumumab is a recombinant, fully humanized IgG2 monoclonal antibody. It binds competitively to the extracellular domain of epidermal growth factor receptor (EGFR) on normal or tumour cells, and thus inhibits ligand-induced receptor autophosphorylation and pathway activation. The KRAS gene encodes a protein involved in signal transduction. Patients with mutated KRAS colorectal tumours do not appear to benefit from EGFR monoclonal antibody inhibitor therapy.

 

 
Distribution

 

After IV administration, panitumumab demonstrates two-compartmental pharmacokinetics.  Pharmacokinetics are non-linear at lower doses until receptor saturation occurs, but is dose-proportional at doses > 2mg/kg. Steady state reached after 3 doses q2w.  Age, gender, tumour type, race, hepatic function, renal function, EGFR membrane expression do not appear to affect panitumumab pharmacokinetics.

 

Cross blood brain barrier?low levels
PPBNo information found
Metabolism
Active metabolitesnone
Inactive metabolitesnone
Elimination

 

Eliminated via the reticuloendothelial system, or bound to EGFR (saturable pathway) to be internalized and degraded.

 

Half-life7.5 days
 
C - Indications and Status
Health Canada Approvals:
 
  • In combination with FOLFOX chemotherapy for the treatment of previously untreated patients with RAS wild-type (non-mutated) metastatic colorectal cancer (mCRC).*
  • As monotherapy for the treatment of patients with EGFR expressing, RAS wild-type mCRC after failure of fluoropyrimidine, oxaliplatin and irinotecan-containing chemotherapy regimens.

Notes:

Panitumumab is NOT indicated for patients with RAS mutant mCRC or for whom RAS mutation status is unknown.


 
 
D - Adverse Effects

Emetogenic Potential:  

Minimal

 

Extravasation Potential:   None

 

 

The following side effects were mainly observed in the pivotal colorectal trial in RAS WT patients where the incidence was >1% higher than the control arm.

 

ORGAN SITESIDE EFFECT* (%)ONSET**
CardiovascularHypertension (5%)E
 Venous thromboembolism (<1%)E
DermatologicalAbnormal eyelash growth (10%)D
 Hand-foot syndrome (2%)E
 Other (24%) (skin fissures)E
 Paronychia (33%)E
 Rash (92%) (acneiform, may be severe)E
 Soft tissue necrosis (skin necrosis; rare)E
GastrointestinalAbdominal pain (27%)E
 Anorexia (30%)E
 Constipation (24%)E
 Diarrhea (24%) (may be severe)E
 Gastritis (2%)E
 GI obstruction (7%)E
 Mucositis (7%)E
 Nausea, vomiting (18%)I
 Weight loss (6%)E
GeneralEdema (11%)E
 Fatigue (33%)E
HematologicalAnemia (7%)E
 Hemorrhage (5%) (including hemoptysis, epistaxis)E
Hepatobiliary↑ LFTs (7%)E
HypersensitivityHypersensitivity (3%) (<1% severe)I
Metabolic / EndocrineAbnormal electrolyte(s) (41%) (↓Mg, Ca, K; severe 5%)E  D
MusculoskeletalMusculoskeletal pain (13%)E
Nervous SystemDepression (5%)E
 Insomnia (5%)E
 Paresthesia (3%)E
OphthalmicConjunctivitis (4%)E
 Keratitis (may be ulcerative - rare)E
RenalRenal failure (2%)E
RespiratoryCough, dyspnea (20%)E
 Pneumonitis (rare)D
UrinaryUrinary symptoms (4%)E


* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

The most common side effects for panitumumab include rash, abnormal electrolyte(s), fatigue, paronychia, anorexia, abdominal pain, constipation, diarrhea, cough and dyspnea.

Increased toxicity and decreased overall survival has been reported in combination with bevacizumab and chemotherapy.

A typical acneiform rash is seen in most patients (92%). Paronychia and skin fissures are also seen. Complications such as infection, necrotizing fasciitis, sepsis (death in rare cases), and local abscesses requiring drainage have been reported. Most commonly affected sites included the face, upper back and chest, and sometimes in the extremities. The median time of developing dermatologic toxicity was 10 days, and the median time to resolution after discontinuing panitumumab was 28 days. As sun exposure may exacerbate skin reactions, patients should be advised to use sunscreen, wear a hat and limit sun exposure. Skin moisturizer applied to the face, hands, feet, neck, back and chest, sunscreen to exposed areas (SPF 30, UVA and UVB) in the morning, hydrocortisone 1% cream at bedtime and doxycycline (or minocycline) have been shown to be of benefit (in a randomized phase 2 study) when used from day -1 to week 6.  Refer to the Canadian recommendations for the management of skin rash during EGFR-targeted monoclonal antibody treatment for GI malignancies (Melosky 2009).

Rare cases of severe rash including Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported, presenting within 7-14 days of starting treatment. Panitumumab should be discontinued.

Interstitial Lung Disease (ILD) is a rare but possibly fatal adverse event with EGFR inhibitors. Patients with acute or worsening respiratory symptoms should have panitumumab held pending diagnosis. If ILD, lung infiltrates, or pneumonitis is confirmed, panitumumab should be discontinued. Patients with history of pulmonary fibrosis or interstitial pneumonitis may have increased risks of developing ILD.

Less than 1% of patients experienced severe (grade 3 to 4) infusion reactions, characterized by anaphylaxis, angioedema, bronchospasm, fever, chills, and hypotension.  Fatal or late reactions (>24 h after infusion) have been reported.

Hypomagnesemia of any grade occurred at various time points during treatment and may be progressive and associated with hypocalcemia and/or hypokalemia.  Serious cases occurred 6 weeks or longer after start of panitumumab. Most grade 3 or higher hypomagnesemic patients received IV electrolyte supplementation. Hypocalcemia was also observed in less than 1% of patients with hypomagnesemia. Electrolytes should be monitored periodically during and for 8 weeks after the end of panitumumab treatment.

Ocular toxicities have been reported, including severe cases of keratitis and ulcerative keratitis.

Neutralizing antibodies develop in <1% of patients (excluding pre-dose and transient positive patients) and do not appear to be clinically relevant.

 

 
E - Dosing
 

Refer to protocol by which patient is being treated.  RAS testing must be complete prior to dosing. Panitumumab is not indicated for patients with RAS mutant mCRC or for whom RAS mutation status is unknown.


 
Adults:
 

No loading dose or premedications are required.

Intravenous: 6 mg/kg every 14 days
 
Dosage with Toxicity:
 

Toxicity

Action

Dose Modification (% previous dose)

≥ grade 3 skin (1st occurrence)

Hold until ≤ grade 2*

Restart at 100%

≥ grade 3 skin (2nd occurrence)Hold until ≤ grade 2*Restart at 80%
≥ grade 3 skin (3rd occurrence)Hold until ≤ grade 2*Restart at 60%
≥ grade 3 skin (4th occurrence)Discontinuen/a

Skin or soft tissue with severe or life-threatening inflammatory or infectious complications

Hold or discontinue, depending on severity

n/a

SJS/TEN                   Discontinuen/a

≥ grade 3 diarrhea or dehydration

Hold until ≤ grade 2

Consider dose reduction, if appropriate

ILD/pneumonitis

Hold and investigate

If confirmed, discontinue. 

Keratitis or ulcerative keratitis

Hold or discontinue, depending on severity or persistence

n/a

*Hold for 1 to 2 doses until recovery. Discontinue if no recovery within 4 weeks.

 

Management of Infusion-related reactions:

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.

 

GradeManagementRe-challenge
1 or 2
  • Stop or slow the infusion.
  • Manage the symptoms.
     

Restart:

  • Restart the infusion at 50% of the rate at which the IR occurred.
  • Re-challenge the infusion at 50% of the rate at which the IR occurred.
3 or 4
  • Stop the infusion.
  • Aggressively manage symptoms.
  • Discontinue permanently (do not re-challenge).

 
Dosage with Hepatic Impairment:
 

The safety and efficacy of panitumumab have not been studied in hepatic impairment.


 
Dosage with Renal Impairment:
 

The safety and efficacy of panitumumab have not been studied in renal impairment. Acute renal failure has been observed in patients experiencing severe diarrhea and dehydration (see dosage with toxicity table for management).


 
Dosage in the elderly:
 

No overall differences in safety or efficacy were observed in patients aged 65 and older compared to younger patients. No dose modifications are required, however patients ≥ 65 years have more eye, skin, GI toxicities and fatigue, compared to younger patients when receiving panitumumab as a single agent or in combination with FOLFOX.


 
Children:
 

The safety and efficacy of panitumumab in pediatric patients have not been established.


 
 
F - Administration Guidelines
 
  • DO NOT ADMINISTER AS AN IV PUSH OR BOLUS; MUST be administered using an IV infusion pump.
  • Diluted with 0.9% sodium chloride only.  Do not mix with other drugs or IV solutions. 
  • Dilute in a total volume of 100mL in sodium chloride 0.9% (Final concentration must be less than 10mg/mL). Infuse IV over 60 minutes. May give via peripheral line or in-dwelling catheter. If the first infusion is tolerated, subsequent infusions may be given over 30 to 60 minutes.
  • Doses higher than 1000mg should be diluted in 150mL 0.9% sodium chloride injection, and infused IV over 90 minutes.
  • Compatible with 0.9% sodium chloride in PVC bags or polyolefin bags
  • Administer using a low-protein binding 0.2 micron or 0.22 micron in-line filter.
  • Solution may contain a small amount of visible, amorphous, panitumumab particulates that will be removed by the low protein binding in-line filter during infusion.
  • Do not shake. Mix diluted solution by gentle inversion.
  • Flush line before and after administration with 0.9% sodium chloride.
  • Keep vials refrigerated in the original carton. Protect from direct sunlight and do not freeze.
  • The manufacturer recommends diluted solutions to be used within 6 hours of preparation if stored at room temperature, or within 24 hours of dilution if stored at 2° to 8°C.
     

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
 


 
 
G - Special Precautions
Contraindications:

 

  • Patients who have a hypersensitivity to this drug or any of its components

     

 

Other Warnings/Precautions:

 

  • Use with caution in patients with a history of pulmonary fibrosis or ILD.
  • It should not be used in combination with bevacizumab and chemotherapy due to unacceptable toxicity, including deaths and shorter survival.
  • In a phase III panitumumab trial, patients with ECOG 2 had increased toxicity and shortened survival compared to those with ECOG 0-1. Assess risk vs. benefit prior to treatment in patients with ECOG 2. 
  • Use with caution in patients with a history of keratitis, ulcerative keratitis, or severe dry eye. Contact lens use is also a risk factor for keratitis and ulceration.
  • If patients experience treatment-related effects on vision and/or ability to concentrate and react, they should not drive or operate machinery until the effect subsides.
  • The panitumumab formulation contains 0.15 mmol sodium (= 3.45 mg sodium) per mL of concentrate. This sodium content should be taken into consideration in patients on sodium restriction.

 


Other Drug Properties:

 

  • Carcinogenicity: Unknown

 

Pregnancy and Lactation:
  • Fetotoxicity: Yes
  • Crosses placental barrier: Yes

    Panitumumab is CONTRAINDICATED in pregnancy as it may cause fetal harm.  Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose. 

  • Fertility effects: Probable
  • Breastfeeding: Not recommended

    As maternal IgG is excreted in milk, discontinue breastfeeding during panitumumab therapy and for 2 months following the last dose.

 
H - Interactions

 

Interactions with other drugs, food, herbal products, and laboratory tests have not been established.

 

 
I - Recommended Clinical Monitoring

 

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

 

Recommended Clinical Monitoring
 
Monitor TypeMonitor Frequency
Clinical pulmonary examBaseline and clinically as indicated

Electrolytes (including calcium, magnesium and potassium)

Baseline and at each visit, until 8 weeks after completion of therapy

Liver function tests

Baseline and before each dose

Renal function tests

Baseline and before each dose

CBC

Baseline and before each dose

Clinical toxicity assessment (including infusion reactions, dermatological, gastrointestinal, pulmonary, ophthalmic).

At each visit
 

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

 
Suggested Clinical Monitoring
 
Monitor TypeMonitor Frequency
Pulmonary function testsBaseline
 
J - Supplementary Public Funding

New Drug Funding Program (NDFP Website )

  • Panitumumab - Metastatic Colorectal Small Bowel or Appendiceal Cancer
  • Panitumumab - In Combination with Chemotherapy for First Line Metastatic Colorectal Small Bowel or Appendiceal Cancer

 

 
K - References

 

Product Monograph: Vectibix® (Panitumumab). Amgen Canada, March 2017.

Vectibix® (Panitumumab) Prescribing Information. Amgen USA, August 2012.

Kang P et al. Infusion-Related and Hypersensitivity Reactions of Monoclonal Antibodies Used to Treat Colorectal Cancer—Identification, Prevention, and Management. Journal of Supportive Oncology 2007; 5(9): 451-7.

Lacouture, ME, Mitchell EP, Piperdi B et al. Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-emptive skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol 2010; 28: 1351-7.

Melosky B, Burkes R, Rayson D, et al. Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Current Oncology 2009; 16(10): 14-24.

Schwartzberg LS, Rivera F, Karthaus M, et al.  PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer.  J Clin Oncol 2014;32(21):2240-7.

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.

 

 

September 2019 Updated infusion reaction information in Dosing section.

 
L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.