Vectibix

Black Box Warnings

Dermatologic toxicity

• Dermatologic toxicities, some severe (NCI-CTC grade 3 or higher), related to panitumumab blockade of EGF binding and subsequent inhibition of EGFR-mediated signaling pathways have been reported in patients receiving panitumumab monotherapy
• Dermatologic toxicities were reported in 90% of patients and were severe in 15% of patients receiving monotherapy
• Clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures
• Severe dermatologic toxicities were complicated by infection including sepsis, septic death, and abscesses requiring incisions and drainage
• It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (eg, Stevens Johnson syndrome or toxic epidermal necrolysis)
• Withhold or discontinue panitumumab and monitor for inflammatory or infectious sequelae in patients with severe dermatologic toxicities

Contraindications

None

Cautions

Increased tumor progression, increased mortality, or lack of benefit in patients with RAS-mutant mCRC; determine RAS-mutant tumor status in an experienced laboratory using an FDA-approved test before treatment

Monitor patients who develop dermatologic toxicities while receiving panitumumab for the development of inflammatory or infectious sequelae; limit sun exposure

Panitumumab is not indicated for use in combination with chemotherapy due to increase in mortality or toxicity

Permanently discontinue in patients developing pulmonary fibrosis/interstitial lung disease

Monitor for keratitis or ulcerative keratitis; interrupt or discontinue panitumumab for acute or worsening keratitis

Monitor electrolytes and institute appropriate treatment if needed

Terminate the infusion for severe infusion reactions

Ocular toxicities reported; monitor for keratitis or ulcerative keratitis; interrupt or discontinue for acute or worsening keratitis

Discontinue permanently if patient develops interstitial lung disease, pneumonitis, or lung infiltrates

Avoid pregnancy

Not indicated for 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 (RAS)

Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia reported; monitor patients for hypomagnesemia and hypocalcemia prior to initiating treatment, periodically during treatment, and for up to 8 weeks after completion of treatment; other electrolyte disturbances, including hypokalemia, have also been observed; replete magnesium and other electrolytes as appropriate

Vectibix is a prescription medication used to treat certain types of colon and rectal cancers that have spread to other parts of the body. Vectibix belongs to a group of drugs called monoclonal antibodies. It works by stopping or slowing the growth of cancer cells.

This medication is available as a solution (liquid) given by an infusion (injected into a vein). The infusion is typically given at an infusion center or clinic and is usually given every two weeks.

Common side effects of Vectibix include tiredness, nausea, vomiting, diarrhea, and skin problems such as rash. It can also cause skin reactions that may be severe, so talk to your doctor or pharmacist if you notice any skin changes such as: pimples, rashes, itching, or redness around the toenails or fingernails.

Vectibix is a prescription medication used to treat certain types of colon and rectal cancer that have spread to other parts of the body.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Vectibix including the following:

Serious skin and subcutaneous tissue reactions. Those experiencing skin and subcutaneous tissue (the layer below the skin) reactions may experience redness, itching, acne, acneiform dermatitis (severe inflammation of the skin that resembles acne), rash, skin fissures (folds or tears in the skin), dry skin, skin exfoliation (loss of cells from the top layer of the skin), or skin ulcers when receiving Vectibix. Talk to your doctor or pharmacist if you notice any changes to your skin.

Paronychia. Paronychia is redness or swelling around the edges of fingernails or toenails caused by an infection.

Increased Sensitivity to Sunlight. Exposure to sunlight may cause your skin to become irritated. Limit going out into the sunlight as much as possible during treatment with Vectibix. When you do go outside, use sunscreen or wear a hat and long sleeves to protect yourself from the sun's rays.  

Allergic Reactions. Symptoms of a severe allergic reaction can include difficulty breathing and swelling of the lips, tongue, or throat. Tell your doctor if you are allergic to Vectibix, or any other medications.

Lung Disease. Vectibix has the potential to cause serious lung disease. Tell your doctor if you have ever had lung disease.

Acute Kidney Failure. Acute (sudden and short-term) kidney failure has occurred in patients receiving Vectibix along with other chemotherapy (medicines that stop or slow the growth of cancer cells). 

Infusion Reactions. Vectibix may cause fever, chills, difficulty breathing, or low blood pressure during the infusion (when injected into a vein). Tell your doctor, pharmacist or nurse in the clinic if you experience any of these symptoms. Your doctor may provide other medications to prevent infusion reactions.

Ocular Keratitis. Vectibix may cause serious ocular (eye) problems that may lead to corneal perforation (a hole in the outer layer of the eye). Tell your doctor or pharmacist right away if you notice any changes in your vision such as blurriness.

Keep all appointments with your doctor. You may require additional appointments for lab tests prior to receiving a dose of Vectibix.

Your doctor may require a test to determine if this medication will be useful for your specific cancer type.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

General

• Premedication to minimize the risk of infusion-related reactions does not appear to be necessary; however, appropriate medical resources for the treatment of severe reactions should be available during panitumumab infusions.1 7 8 9 15 19 22

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 Do not administer by rapid IV injection (e.g., IV push or “bolus”).1

Solution should be colorless and may contain a small amount of visible, translucent-to-white, amorphous, proteinaceous particulates of panitumumab; do not administer if discoloration observed.1

Do not shake vials.1

Use infusion pump to administer.1 Prior to and following administration, flush line with 0.9% sodium chloride injection.1 Administer drug through a low-protein-binding 0.2- or 0.22-mcm inline filter.1

Withdraw appropriate dose of panitumumab injection solution (containing 20 mg/mL) and dilute in 0.9% sodium chloride injection to a total volume of 100 mL; doses >1 g should be diluted in 0.9% sodium chloride injection to a total volume of 150 mL.1 Final concentration should not exceed 10 mg of panitumumab per mL.1

Mix diluted solution by gentle inversion; do not shake.1

Do not mix or dilute panitumumab with other drugs or infusion solutions.1

Administer over 60 minutes if dose is ≤1 g; administer over 90 minutes if dose is >1 g.1

Dosage

Adults

For the management of previously treated, EGFR-expressing metastatic colorectal cancer as monotherapy, 6 mg/kg over 60 minutes every 14 days.1 2 4 9 13 Doses >1 g should be infused over 90 minutes.1 2 9 In the randomized controlled trial evaluating panitumumab monotherapy for metastatic colorectal cancer, a median of 5 doses was administered.1

Dosage Modification for Toxicity

If mild or moderate (grade 1 or 2) infusion-related reactions occur, reduce infusion rate by 50% for the duration of that infusion.1 9

If severe (grade 3 or 4) infusion-related reactions occur, discontinue therapy immediately and permanently.1 9 15

If severe (grade 3 or 4) or intolerable dermatologic toxicity occurs, withhold therapy.1 If toxicity does not improve to ≤ grade 2 within 1 month, permanently discontinue therapy.1

If dermatologic toxicity improves to ≤ grade 2 and patient is symptomatically improved after withholding no more than 2 doses, resume treatment at 50% of the original dosage.1 Dosage may then be increased in increments of 25% of the original dosage up to the recommended dosage of 6 mg/kg if toxicity does not recur.1 If toxicity recurs, permanently discontinue therapy.1

Special Populations

No special population dosage recommendations at this time.1

No formal drug interaction studies have been performed.1 16

Specific Drugs or Therapies

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Anxiety
• bloating or swelling of the face, arms, hands, lower legs, ankles, or feet
• chest pain
• chills
• confusion
• constipation
• convulsions
• cough
• decreased urination
• deep cracks, grooves, or lines in the skin
• diarrhea
• difficulty with swallowing
• discoloration of the fingernails or toenails
• drowsiness
• dry mouth, lips, or skin
• fainting
• fast or irregular heartbeat
• fever
• flushing or redness of the skin
• increased thirst
• itching, pain, and swelling of the eyelid
• itching, skin rash
• loosening of the fingernails
• loss of appetite
• muscle pain or cramps
• muscle spasms or twitching
• nausea
• rapid weight gain
• rapid, shallow breathing
• redness or soreness around the fingernails
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• stomach pain
• sunken eyes
• swelling or inflammation of the mouth
• tearing of the eyes
• tingling of the hands or feet
• trembling
• troubled breathing
• unusual tiredness or weakness
• unusual weight gain or loss
• unusually warm skin
• vomiting

• Blurred vision
• burning, dry, or itching eyes
• discharge from the eyes or excessive tearing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• facial swelling
• headache
• hives
• noisy breathing
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• sweating
• swelling of the eye, eyelid, or inner lining of the eyelid
• tightness in the chest

• Chest discomfort
• painful breathing
• quick, shallow breathing
• slight fever

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, or warmth at the injection site
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take Vectibix. This includes your doctors, nurses, pharmacists, and dentists.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Have an eye exam as you have been told by your doctor.
• Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects from the sun while taking this medicine and for at least 2 months after care ends.
• Very bad and sometimes deadly side effects have happened during the infusion. Tell your doctor if you have any bad effects during the infusion.
• Very bad loose stools (diarrhea) and fluid loss (dehydration) have happened with Vectibix when used with chemo drugs. This can lead to kidney problems or other health problems. Talk with your doctor.
• Blood clots have happened with this medicine. Sometimes, these blood clots have been deadly. Talk with the doctor.
• People with a certain gene mutation (RAS) may not benefit from Vectibix. Their tumor may also get worse and chance of death may be raised. Talk with the doctor.
• If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during care and for 6 months after care ends. Use birth control that you can trust.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust during care and for 6 months after care ends.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use Vectibix as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Vectibix (panitumumab) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Vectibix. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Injection: 100 mg/5 mL (20 mg/mL) colorless solution in single-dose vial.

Injection: 400 mg/20 mL (20 mg/mL) colorless solution in single-dose vial.

      Mechanism of Action

The EGFR is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases, including EGFR, HER2, HER3, and HER4. EGFR is constitutively expressed in normal epithelial tissues, including the skin and hair follicle.  EGFR is overexpressed in certain human cancers, including colon and rectum cancers.  Interaction of EGFR with its normal ligands (e.g., EGF, transforming growth factor-alpha) leads to phosphorylation and activation of a series of intracellular proteins, which in turn regulate transcription of genes involved with cellular growth and survival, motility, and proliferation.  KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) and NRAS (Neuroblastoma RAS viral oncogene homologue) are highly related members of the RAS oncogene family.  Signal transduction through the EGFR can result in activation of the wild-type KRAS and NRAS proteins; however, in cells with activating RAS somatic mutations, the RAS-mutant proteins are continuously active and appear independent of EGFR regulation.

Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR.  Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased proinflammatory cytokine and vascular growth factor production, and internalization of the EGFR.  In vitro assays and in vivo animal studies demonstrate that panitumumab inhibits the growth and survival of selected human tumor cell lines expressing EGFR.

      Pharmacokinetics

Panitumumab administered as a single agent exhibits nonlinear pharmacokinetics.

Following single-dose administrations of panitumumab as 1-hour infusions, the area under the concentration-time curve (AUC) increased in a greater than dose-proportional manner, and clearance (CL) of panitumumab decreased from 30.6 to 4.6 mL/day/kg as the dose increased from 0.75 to 9 mg/kg.  However, at doses above 2 mg/kg, the AUC of panitumumab increased in an approximately dose-proportional manner.

Following the recommended dose regimen (6 mg/kg given once every 2 weeks as a 1-hour infusion), panitumumab concentrations reached steady-state levels by the third infusion with mean (± SD) peak and trough concentrations of 213 ± 59 and 39 ± 14 mcg/mL, respectively. The mean (± SD) AUC0-tau and CL were 1306 ± 374 mcg•day/mL and 4.9 ± 1.4 mL/kg/day, respectively.  The elimination half-life was approximately 7.5 days (range: 3.6 to 10.9 days).

A population pharmacokinetic analysis was performed to explore the potential effects of selected covariates on panitumumab pharmacokinetics.  Results suggest that age (21-88 years), gender, race (15% nonwhite), mild-to-moderate renal dysfunction, mild-to-moderate hepatic dysfunction, and EGFR membrane-staining intensity (1+, 2+, and 3+) in tumor cells had no apparent impact on the pharmacokinetics of panitumumab.

No formal pharmacokinetic studies of panitumumab have been conducted in patients with renal or hepatic impairment.

      Recurrent or Refractory mCRC

The safety and efficacy of Vectibix was demonstrated in Study 20020408, an open-label, multinational, randomized, controlled trial of 463 patients with EGFR-expressing, metastatic carcinoma of the colon or rectum, in Study 20080763, an open-label, multicenter, multinational, randomized trial of 1010 patients with wild-type KRAS mCRC, and in Study 20100007, an open-label, multicenter, multinational, randomized trial of 377 patients with wild-type KRAS mCRC.

Study 20020408 (NCT00113763)

Patients in Study 20020408 were required to have progressed on or following treatment with a regimen(s) containing a fluoropyrimidine, oxaliplatin, and irinotecan; progression was confirmed by an independent review committee (IRC) masked to treatment assignment for 76% of the patients. Patients were randomized (1:1) to receive panitumumab at a dose of 6 mg/kg given once every 2 weeks plus BSC (N = 231) or BSC alone (N = 232) until investigator-determined disease progression. Randomization was stratified based on Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0 and 1 vs 2) and geographic region (Western Europe, Eastern/Central Europe, or other). Upon investigator-determined disease progression, patients in the BSC-alone arm were eligible to receive panitumumab and were followed until disease progression was confirmed by the IRC.

Based upon IRC determination of disease progression, a statistically significant prolongation in PFS was observed in patients receiving panitumumab compared to those receiving BSC alone. The mean PFS was 96 days in the panitumumab arm and 60 days in the BSC-alone arm.

The study results were analyzed in the wild-type KRAS subgroup where KRAS status was retrospectively determined using archived paraffin-embedded tumor tissue.  KRAS mutation status was determined in 427 patients (92%); of these, 243 (57%) had no detectable KRAS mutations in either codons 12 or 13. The hazard ratio for PFS in patients with wild-type KRAS mCRC was 0.45 (95% CI: 0.34-0.59) favoring the panitumumab arm.  The response rate was 17% for the panitumumab arm and 0% for BSC. There were no differences in OS; 77% of patients in the BSC arm received panitumumab at the time of disease progression.

Study 20080763 (NCT01001377)

Study 20080763 was an open-label, multicenter, multinational, randomized (1:1) clinical trial, stratified by region (North America, Western Europe, and Australia versus rest of the world) and ECOG PS (0 and 1 vs 2) in patients with wild-type KRAS mCRC. A total of 1010 patients who received prior treatment with irinotecan, oxaliplatin, and a thymidylate synthase inhibitor were randomized to receive Vectibix 6 mg/kg intravenously over 60 minutes every 14 days or cetuximab 400 mg/m2 intravenously over 120 minutes on day 1 followed by 250 mg/m2 intravenously over 60 minutes every 7 days. The trial excluded patients with clinically significant cardiac disease and interstitial lung disease.  The major efficacy analysis tested whether the OS of Vectibix was noninferior to cetuximab. Data for investigator-assessed PFS and objective response rate (ORR) were also collected. The criteria for noninferiority was for Vectibix to retain at least 50% of the OS benefit of cetuximab based on an OS hazard ratio of 0.55 from the NCIC CTG CO.17 study relative to BSC.

In Study 20080763, 37% of patients were women, 52% were white, 45% were Asian, and 1.3% were Hispanic or Latino.  Thirty-one percent of patients were enrolled at sites in North America, Western Europe, or Australia. ECOG performance was 0 in 32% of patients, 1 in 60% of patients, and 2 in 8% of patients. Median age was 61 years. More patients (62%) had colon cancer than rectal cancer (38%). Most patients (74%) had not received prior bevacizumab.

The key efficacy analysis for Study 20080763 demonstrated that Vectibix was statistically significantly noninferior to cetuximab for OS.

The efficacy results for Study 20080763 are presented in Table 3 and Figure 1.

a Modified intent-to-treat population that included all patients who received at least one dose of therapy

Figure 1:  Kaplan-Meier Plot of Overall Survival in Patients with Wild-type KRAS mCRC (Study 20080763)

Study 20100007 (NCT01412957)

Study 20100007 was an open-label, multicenter, randomized (1:1) clinical study stratified by ECOG performance status (0 or 1 vs 2) and region (sites in Europe versus Asia versus rest of world) in patients with wild-type KRAS mCRC. Eligible patients were required to have received prior therapy with irinotecan, oxaliplatin, and a thymidylate synthase inhibitor, and have wild-type KRAS exon 2 mCRC as determined by a clinical trial assay.  An assessment for RAS status (defined as KRAS exons 2, 3, and 4 and NRAS exons 2, 3, and 4) using Sanger sequencing was conducted in patients for whom tumor tissue was available.

Patients were randomized to receive Vectibix (6 mg/kg intravenously every 14 days) plus BSC or BSC alone.  Patients received Vectibix and BSC or BSC until disease progression, withdrawal of consent, unacceptable toxicity, or death.  Patients randomized to BSC were not offered Vectibix at the time of disease progression. The major efficacy outcome measure was OS in patients with wild-type KRAS mCRC. Secondary efficacy outcome measures included OS in the subgroup of patients with wild-type RAS mCRC; PFS and ORR in patients with wild-type KRAS; and PFS and ORR in the subgroup of patients with wild-type RAS mCRC.

A total of 377 patients were randomized, 189 to the Vectibix plus BSC arm and 188 to the BSC alone arm.  Baseline demographics and disease characteristics were: median age of 61 years (range 19, 82); 57% male; 55% White, 43% Asian; 36% ECOG PS-0, 55% ECOG PS-1; 57% had a primary colon tumor and 43% had a primary rectal tumor; and 32% had prior bevacizumab exposure.

KRAS tumor mutation status was available for all patients and RAS tumor mutation status was available for 86% of the 377 patients. Among the 377 patients, 270 (72%) patients had wild-type RAS tumors, 54 (14%) had mutant RAS tumors, and 54 (14%) had unknown RAS tumor status.

The results of the study demonstrated a statistically significant improvement in overall survival.  The efficacy results for Study 20100007 are presented in Table 4 and Figure 2.

Figure 2:  Kaplan-Meier Plot of Overall Survival in Patients with Wild-type RAS mCRC (Study 20100007)

      First-line in Combination with FOLFOX Chemotherapy

Study 20050203 (NCT00364013)

Study 20050203 was a multicenter, open-label trial that randomized (1:1) patients with mCRC who were previously untreated in the metastatic setting and who had received no prior oxaliplatin to receive Vectibix every 14 days in combination with FOLFOX or to FOLFOX alone every 14 days. Vectibix was administered at 6 mg/kg over 60 minutes prior to administration of chemotherapy. The FOLFOX regimen consisted of oxaliplatin 85 mg per m2 IV infusion over 120 minutes and leucovorin (dl-racemic) 200 mg per m2 intravenous infusion over 120 minutes at the same time on day 1 using a Y-line, followed on day 1 by 5-FU 400 mg per m2 intravenous bolus.  The 5-FU bolus was followed by a continuous infusion of 5-FU 600 mg per m2 over 22 hours.  On day 2, patients received leucovorin 200 mg per m2 followed by the bolus dose (400 mg per m2) and continuous infusion of 5-FU (600 mg per m2) over 22 hours.  Study 20050203 excluded patients with known central nervous system metastases, clinically significant cardiac disease, interstitial lung disease, or active inflammatory bowel disease. The prespecified major efficacy measure was PFS in the subgroup of patients with wild-type KRAS mCRC as assessed by a blinded independent central review of imaging. Other key efficacy measures included OS and ORR.

In Study 20050203, in the wild-type KRAS subgroup (n = 656), 64% of patients were men, 92% White, 2% Black, and 4% Hispanic or Latino.  Sixty-six percent of patients had colon cancer and 34% had rectal cancer. ECOG performance was 0 in 56% of patients, 1 in 38% of patients, and 2 in 6% of patients. Median age was 61.5 years.

The efficacy results in Study 20050203 in patients with wild-type KRAS mCRC are presented in Table 5 below.

Exploratory Analysis of OS

An exploratory analysis of OS with updated information based on events in 82% of patients with wild-type KRAS mCRC estimated the treatment effect of Vectibix plus FOLFOX compared with FOLFOX alone on OS (Figure 3). Median OS among 325 patients with wild-type KRAS mCRC who received Vectibix plus FOLFOX was 23.8 months (95% CI: 20.0, 27.7) vs 19.4 months (95% CI: 17.4, 22.6) among 331 patients who received FOLFOX alone (HR = 0.83, 95% CI: 0.70, 0.98).

Figure 3:  Kaplan-Meier Plot of Overall Survival in Patients with Wild-type KRAS mCRC (Study 20050203)

Retrospective exploratory analyses in the RAS wild-type subgroup

Among the 656 patients with wild-type KRAS exon 2 mCRC, RAS mutation status was assessed for 620 patients using Sanger bidirectional sequencing and Surveyor®/WAVE® analysis.  Of these 620 patients, approximately 17% of patients (n = 104) tumors harbored mutations in KRAS exons 3 or 4 or in NRAS exons 2, 3, and 4.

Retrospective subset analyses were then conducted among the subset of patients without RAS mutations (n = 512) as described above.

In the wild-type RAS subgroup, 65% of patients were men and 91% were White, 2% Black, and 5% Hispanic or Latino. Sixty-five percent of patients had colon cancer and 35% had rectal cancer. ECOG performance was 0 in 57% of patients, 1 in 37% of patients, and 2 in 6% of patients. Median age was 61 years.

*OS with updated information based on events in 82% of patients

Figure 4: Kaplan Meier Plot of Overall Survival in Patients with Wild-Type RAS-mCRC (Study 20050203)

      RAS-Mutant mCRC

Vectibix is not effective for the treatment of patients with RAS-mutant mCRC, 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.

In Study 20050203, among patients with RAS-mutant tumors, the median PFS was 7.3 months (95% CI: 6.3, 7.9) among 272 patients receiving Vectibix plus FOLFOX and 8.7 months (95% CI: 7.6, 9.4) among patients who received FOLFOX alone (HR = 1.31, 95% CI: 1.07, 1.60). The median OS was 15.6 months (95% CI: 13.4, 17.9) among patients receiving Vectibix plus FOLFOX and 19.2 months (95% CI: 16.7, 21.8) among patients who received FOLFOX alone (HR = 1.25, 95% CI: 1.02, 1.55).

In Study 20100007, among patients with RAS-mutant tumors, no differences in OS or PFS were observed between the treatment arms [n = 54; OS HR = 0.99 (95% CI: 0.49, 2.00); PFS HR = 1.03 (95% CI: 0.56, 1.90)].

Call your doctor for instructions if you miss an appointment for your Vectibix injection.