1. Name Of The Medicinal Product
Vectibix®
2. Qualitative And Quantitative Composition
Each ml of concentrate contains 20 mg panitumumab.
Each vial contains either 100 mg of panitumumab in 5 ml, 200 mg in 10 ml, or 400 mg in 20 ml.
When prepared according to the instructions given in section 6.6, the final panitumumab concentration should not exceed 10 mg/ml.
Panitumumab is a fully human monoclonal IgG2 antibody produced in a mammalian cell line (CHO) by recombinant DNA technology.
Excipient:
Each ml of concentrate contains 0.150 mmol sodium, which is 3.45 mg sodium.
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Concentrate for solution for infusion (sterile concentrate).
Colourless solution that may contain, translucent to white, visible amorphous, proteinaceous panitumumab particles.
4. Clinical Particulars
4.1 Therapeutic Indications
Vectibix is indicated for the treatment of patients with wild-type KRAS metastatic colorectal cancer (mCRC):
• in first-line in combination with FOLFOX
• in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan).
• as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
4.2 Posology And Method Of Administration
Vectibix treatment should be supervised by a physician experienced in the use of anti-cancer therapy. Evidence of wild-type KRAS status is required before initiating treatment with Vectibix. KRAS mutational status should be determined using a validated test method by an experienced laboratory.
Posology
The recommended dose of Vectibix is 6 mg/kg of bodyweight given once every two weeks. Prior to infusion, Vectibix should be diluted in 0.9% sodium chloride injection to a final concentration not to exceed 10 mg/ml (for preparation instructions see section 6.6).
The severity of dermatological reactions often correlates with the clinical efficacy of the EGFR inhibitor. For patients who have not developed skin toxicity after 2-4 cycles of therapy, a reassessment of the treatment effect is recommended.
Modification of the dose of Vectibix may be necessary in cases of severe (
Method of administration
Vectibix must be administered as an intravenous (IV) infusion via an infusion pump, using a low protein binding 0.2 or 0.22 micrometer in-line filter, through a peripheral line or indwelling catheter. The recommended infusion time is approximately 60 minutes. If the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes. Doses higher than 1000 mg should be infused over approximately 90 minutes (for handling instructions, see section 6.6).
The infusion line should be flushed with sodium chloride solution before and after Vectibix administration to avoid mixing with other medicinal products or IV solutions.
A reduction in the rate of infusion of Vectibix may be necessary in cases of infusion-related reactions (see section 4.4).
Do not administer as an IV push or bolus.
For instructions on dilution of the medicinal product before administration, see section 6.6.
Special populations
The safety and efficacy of Vectibix have not been studied in patients with renal or hepatic impairment.
There is no clinical data to support dose adjustments in the elderly
Paediatric population
There is no experience in children and Vectibix should not be used in those patients less than 18 years of age.
4.3 Contraindications
Vectibix is contraindicated in patients with a history of severe or life-threatening hypersensitivity reactions to the active substance or to any of the excipients (see section 4.4).
Patients with interstitial pneumonitis or pulmonary fibrosis (see section 4.4).
The combination of Vectibix with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant KRAS mCRC or for whom KRAS mCRC status is unknown.
4.4 Special Warnings And Precautions For Use
Dermatological reactions
Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFR) inhibitors, are experienced with nearly all patients (approximately 90%) treated with Vectibix (see section 4.8), the majority are mild to moderate in nature. If a patient develops dermatologic reactions that are grade 3 (CTCAE v 4.0) or higher, or that are considered intolerable, the following dose modification is recommended:
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1 Greater than or equal to grade 3 is defined as severe or life-threatening
In clinical studies, subsequent to the development of severe dermatological reactions (including stomatitis), infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported. Patients who have severe dermatologic reactions or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae (including cellulitis), and appropriate treatment promptly initiated. Treatment of dermatologic reactions should be based on severity and may include a moisturiser, sun screen (SPF > 15 UVA and UVB), and topical steroid cream (not stronger than 1% hydrocortisone) applied to affected areas, and/or oral antibiotics. It is also recommended that patients experiencing rash/dermatological toxicities wear sunscreen and hats and limit sun exposure as sunlight can exacerbate any skin reactions that may occur.
Proactive skin treatment including skin moisturiser, sun screen (SPF > 15 UVA and UVB), topical steroid cream (not stronger than 1% hydrocortisone) and an oral antibiotic (e.g. doxycycline) may be useful in the management of dermatologic reactions. Patients may be advised to apply moisturiser and sunscreen to face, hands, feet, neck, back and chest every morning during treatment, and to apply the topical steroid to face, hands, feet, neck, back and chest every night during treatment.
Pulmonary complications
Patients with a history of, or evidence of, interstitial pneumonitis or pulmonary fibrosis were excluded from clinical studies. As Interstitial Lung Disease (ILD) has been observed with EGFR inhibitors, in the event of acute onset or worsening pulmonary symptoms, Vectibix treatment should be interrupted and a prompt investigation of these symptoms should occur. If pneumonitis or lung infiltrates are diagnosed, Vectibix should be discontinued and the patient should be treated appropriately.
Electrolyte disturbances
Progressively decreasing serum magnesium levels leading to severe (grade 4) hypomagnesaemia have been observed in some patients. Patients should be periodically monitored for hypomagnesaemia and accompanying hypocalcaemia prior to initiating Vectibix treatment, and periodically thereafter for up to 8 weeks after the completion of treatment (see section 4.8). Magnesium repletion is recommended, as appropriate.
Other electrolyte disturbances, including hypokalaemia, have also been observed. Repletion of these electrolytes is also recommended, as appropriate.
Infusion related reactions
Across monotherapy and combination mCRC clinical studies, infusion-related reactions (occurring within 24 hours of an infusion) were reported in 3% of Vectibix-treated patients, of which <1% were severe (CTCAE v 4.0 grade 3 and grade 4).
In the post-marketing setting, serious infusion-related reactions have been reported, including rare post-marketing reports with a fatal outcome. If a severe or life-threatening reaction occurs during an infusion or at any time post-infusion [e.g. presence of bronchospasm, angioedema, hypotension, need for parenteral medication, or anaphylaxis], Vectibix should be permanently discontinued (see sections 4.3 and 4.8).
In patients experiencing a mild or moderate (CTCAE v 4.0grade 1 and 2) infusion-related reaction the infusion rate should be reduced for the duration of that infusion. It is recommended to maintain this lower infusion rate in all subsequent infusions.
Hypersensitivity reactions occurring more than 24 hours after infusion have been reported including a fatal case of angioedema that occurred more than 24 hours after the infusion. Patients should be informed of the possibility of a late onset reaction and instructed to contact their physician if symptoms of a hypersensitivity reaction occur.
Other precautions
This medicinal product contains 0.150 mmol sodium (which is 3.45 mg sodium) per ml of concentrate. To be taken into consideration by patients on a controlled sodium diet.
Vectibix in combination with irinotecan, bolus 5-flourouracil, and leucovorin (IFL) chemotherapy
Patients receiving Vectibix in combination with the IFL regimen [bolus 5-fluorouracil (500 mg/m2), leucovorin (20 mg/m2) and irinotecan (125 mg/m2)] experienced a high incidence of severe diarrhoea (see section 4.8). Therefore administration of Vectibix in combination with IFL should be avoided (see section 4.5).
Vectibix in combination with bevacizumab and chemotherapy regimens
A randomised, open-label, multicentre study of 1,053 patients evaluated the efficacy of bevacizumab and oxaliplatin- or irinotecan-containing chemotherapeutic regimens with and without Vectibix in the first-line treatment of metastatic colorectal cancer. Shortened progression free survival time and increased deaths were observed in the patients receiving Vectibix in combination with bevacizumab and chemotherapy. A greater frequency of pulmonary embolism, infections (predominantly of dermatologic origin), diarrhoea, electrolyte imbalances, nausea, vomiting and dehydration was also observed in the treatment arms using Vectibix in combination with bevacizumab and chemotherapy. An additional analysis of efficacy data by KRAS status did not identify a subset of patients who benefited from Vectibix in combination with oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. A trend towards worse survival was observed with Vectibix in the wild-type KRAS subset of the bevacizumab and oxaliplatin cohort, and a trend towards worse survival was observed with Vectibix in the bevacizumab and irinotecan cohort regardless of KRAS mutational status. Therefore, Vectibix should not be administered in combination with bevacizumab containing chemotherapy (see sections 4.5 and 5.1).
Vectibix in combination with oxaliplatin-based chemotherapy in patients with mutant KRAS mCRC or for whom KRAS tumour status is unknown
The combination of Vectibix with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant KRAS mCRC or for whom KRAS mCRC status is unknown. In a phase 3 study (n = 1183, 656 patients with wild-type KRAS and 440 patients with mutant KRAS tumours) evaluating panitumumab in combination with infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) compared to FOLFOX alone as first-line therapy for mCRC, a shortened progression-free survival and overall survival time were observed in patients with mutant KRAS tumours who received panitumumab and FOLFOX (n = 221) vs. FOLFOX alone (n = 219).
KRAS mutational status should be determined using a validated test method by an experienced laboratory. If Vectibix is to be used in combination with FOLFOX then it is recommended that mutational status be determined by a laboratory that participates in a KRAS European Quality Assurance program or wild-type status be confirmed in a duplicate test.
Acute renal failure
Acute renal failure has been observed in patients who develop severe diarrhoea and dehydration.
Ocular toxicities
Serious cases of keratitis and ulcerative keratitis have been rarely reported in the post-marketing setting. Patients presenting with signs and symptoms suggestive of keratitis such as acute or worsening: eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye should be referred promptly to an ophthalmology specialist.
If a diagnosis of ulcerative keratitis is confirmed, treatment with Vectibix should be interrupted or discontinued. If keratitis is diagnosed, the benefits and risks of continuing treatment should be carefully considered.
Vectibix should be used 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.
Patients with ECOG 2 performance status treated with Vectibix in combination with chemotherapy
For patients with ECOG 2 performance status, assessment of benefit-risk is recommended prior to initiation of Vectibix in combination with chemotherapy for treatment of mCRC. A positive benefit-risk balance has not been documented in patients with ECOG 2 performance status (see section 5.1).
Elderly Patients
No overall differences in safety or efficacy were observed in elderly patients (
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Data from an interaction study involving Vectibix and irinotecan in patients with mCRC indicated that the pharmacokinetics of irinotecan and its active metabolite, SN-38, are not altered when the drugs are co-administered. Results from a cross-study comparison indicated that irinotecan-containing regimens (IFL or FOLFIRI) have no effect on the pharmacokinetics of panitumumab.
Vectibix should not be administered in combination with IFL chemotherapy or with bevacizumab-containing chemotherapy. A high incidence of severe diarrhoea was observed when panitumumab was administered in combination with IFL (see section 4.4), and increased toxicity and deaths were seen when panitumumab was combined with bevacizumab and chemotherapy (see sections 4.4 and 5.1).
The combination of Vectibix with oxaliplatin-containing chemotherapy is contraindicated for patients with mutant KRAS mCRC or for whom KRAS mCRC status is unknown. A shortened progression-free survival and overall survival time were observed in a clinical study in patients with mutant KRAS tumours who received panitumumab and FOLFOX (see section 4.4 and 5.1).
4.6 Pregnancy And Lactation
Pregnancy
There are no adequate data from the use of Vectibix in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. EGFR has been implicated in the control of prenatal development and may be essential for normal organogenesis, proliferation, and differentiation in the developing embryo. Therefore, Vectibix has the potential to cause foetal harm when administered to pregnant women.
Human IgG is known to cross the placental barrier, and panitumumab may therefore be transmitted from the mother to the developing foetus. In women of childbearing potential, appropriate contraceptive measures must be used during treatment with Vectibix, and for 6 months following the last dose. If Vectibix is used during pregnancy or if the patient becomes pregnant while receiving this medicinal product, she should be advised of the potential risk for loss of the pregnancy or potential hazard to the foetus.
Women who become pregnant during Vectibix treatment are encouraged to enrol in Amgen's Pregnancy Surveillance programme. Contact details are provided in section 6 of the Package Leaflet – Information for the user.
Breast-feeding
It is unknown whether panitumumab is excreted in human breast milk. Because human IgG is secreted into human milk, panitumumab might also be secreted. The potential for absorption and harm to the infant after ingestion is unknown. It is recommended that women do not breast feed during treatment with Vectibix and for 3 months after the last dose.
Fertility
Animal studies have shown reversible effects on the menstrual cycle and reduced female fertility in monkeys (see section 5.3). Panitumumab may impact the ability of a woman to become pregnant.
4.7 Effects On Ability To Drive And Use Machines
No studies on the effects on the ability to drive and use machines have been performed. If patients experience treatment-related symptoms affecting their vision and/or ability to concentrate and react, it is recommended that they do not drive or use machines until the effect subsides.
4.8 Undesirable Effects
Summary of safety profile
Based on an analysis of all mCRC clinical trial patients receiving Vectibix monotherapy and in combination with chemotherapy (n = 2588), the most commonly reported adverse reactions are skin reactions occurring in 93% of patients. These reactions are related to the pharmacologic effects of Vectibix, and the majority are mild to moderate in nature with 25% severe (grade 3 NCI-CTC) and < 1% life threatening (grade 4 NCI-CTC). For clinical management of skin reactions, including dose modification recommendations, see section 4.4.
Commonly reported adverse reactions occurring in
Tabulated summary of adverse reactions
The data in the table below describe adverse reactions reported from clinical studies in patients with mCRC who received panitumumab as a single agent or in combination with chemotherapy (n = 2588). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
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1 Reports of this adverse reaction arose in the post-marketing setting
2 Rash includes common terms of skin toxicity, skin exfoliation, exfoliative rash, rash papular, rash pruritic, rash erythematous, rash generalised, rash macular, rash maculo-papular, skin lesion
The safety profile of Vectibix in combination with chemotherapy consisted of the reported adverse reactions of Vectibix (as a monotherapy) and the toxicities of the background chemotherapy regimen. No new toxicities or worsening of previously recognised toxicities beyond the expected additive effects were observed. Skin reactions were the most frequently occurring adverse reactions in patients receiving panitumumab in combination with chemotherapy. Other toxicities that were observed with a greater frequency relative to monotherapy included hypomagnesaemia, diarrhoea, and stomatitis. These toxicities infrequently led to discontinuation of Vectibix or of chemotherapy.
Description of selected adverse reactions
Gastrointestinal disorders
Diarrhoea when reported was mainly mild or moderate in severity. Severe diarrhoea (NCI-CTC grade 3 and 4) was reported in 2% of patients treated with Vectibix as a monotherapy and in 17% of patients treated with Vectibix in combination with chemotherapy.
There have been reports of acute renal failure in patients who develop diarrhoea and dehydration (see section 4.4).
Infusion related reactions
Across all clinical studies, infusion reactions (occurring within 24 hours of any infusion), which may include symptoms/signs such as chills, fever or dyspnea, were reported in 3% of Vectibix-treated patients, of which < 1% were severe (NCI-CTC grade 3 and grade 4).
A case of fatal angioedema occurred in a patient with recurrent and metastatic squamous cell carcinoma of the head and neck treated with Vectibix in a clinical trial. The fatal event occurred after re-exposure following a prior episode of angioedema; both episodes occurred greater than 24 hours after administration (see sections 4.3 and 4.4). Hypersensitivity reactions occurring more than 24 hours after infusion have also been reported in the post-marketing setting.
For clinical management of infusion-related reactions, see section 4.4.
Skin and subcutaneous tissue disorders
Skin rash most commonly occurred on the face, upper chest, and back, but could extend to the extremities. Subsequent to the development of severe skin and subcutaneous reactions, infectious complications including sepsis, in rare cases leading to death, cellulitis and local abscesses requiring incisions and drainage were reported. The median time to first symptom of dermatologic reaction was 10 days, and the median time to resolution after the last dose of Vectibix was 28 days.
Paronychial inflammation was associated with swelling of the lateral nail folds of the toes and fingers.
Dermatological reactions (including nail effects), observed in patients treated with Vectibix or other EGFR inhibitors, are known to be associated with the pharmacologic effects of therapy.
Across all clinical trials, skin reactions occurred in 93% of patients receiving Vectibix as monotherapy or in combination with chemotherapy (n = 2588). These events consisted predominantly of rash and dermatitis acneiform and were mostly mild to moderate in severity. Severe (NCI-CTC grade 3) skin reactions were reported in 34% and life-threatening (NCI-CTC grade 4) skin reactions in < 1% of patients who received Vectibix in combination with chemotherapy (n = 1536).
For clinical management of dermatological reactions, including dose modification recommendations, see section 4.4.
In the post-marketing setting, cases of skin necrosis have been reported.
Paediatric population
There is no experience in children and Vectibix should not be used in those patients less than 18 years of age.
Other special populations
No overall differences in safety or efficacy were observed in elderly patients (
Ocular toxicities
Non-serious cases of keratitis have been observed in 0.2 to 0.7% of clinical trial patients. In the post-marketing setting, serious cases of keratitis and ulcerative keratitis have been rarely reported (see section 4.4).
The safety of Vectibix has not been studied in patients with renal or hepatic impairment.
4.9 Overdose
Doses up to 9 mg/kg have been tested in clinical trials. There have been reports of overdose at doses up to approximately twice the recommended therapeutic dose (12 mg/kg). Adverse events observed included skin toxicity, diarrhoea, dehydration and fatigue and were consistent with the safety profile at the recommended dose.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies, ATC code: L01XC08
Mechanism of action
Panitumumab is a recombinant, fully human IgG2 monoclonal antibody that binds with high affinity and specificity to the human EGFR. EGFR is a transmembrane glycoprotein that is a member of a subfamily of type I receptor tyrosine kinases including EGFR (HER1/c-ErbB-1), HER2, HER3, and HER4. EGFR promotes cell growth in normal epithelial tissues, including the skin and hair follicle, and is expressed on a variety of tumour cells.
Panitumumab binds to the ligand binding domain of EGFR and inhibits receptor autophosphorylation induced by all known EGFR ligands. Binding of panitumumab to EGFR results in internalisation of the receptor, inhibition of cell growth, induction of apoptosis, and decreased interleukin 8 and vascular endothelial growth factor production.
The KRAS (Kirsten rat sarcoma 2 viral oncogene homologue) gene encodes a small, GTP-binding protein involved in signal transduction. A variety of stimuli, including that from the EGFR activates KRAS which in turn stimulates other intracellular proteins to promote cell proliferation, cell survival and angiogenesis.
Activating mutations in the KRAS gene occur frequently in a variety human tumours and have been implicated in both oncogenesis and tumour progression.
Pharmacodynamic effects
In vitro assays and in vivo animal studies have shown that panitumumab inhibits the growth and survival of tumour cells expressing EGFR. No anti-tumour effects of panitumumab were observed in human tumour xenografts lacking EGFR expression. The addition of panitumumab to radiation, chemotherapy or other targeted therapeutic agents, in animal studies resulted in an increase in anti-tumour effects compared to radiation, chemotherapy or targeted therapeutic agents alone.
Dermatological reactions (including nail effects), observed in patients treated with Vectibix or other EGFR inhibitors, are known to be associated with the pharmacologic effects of therapy (with cross-reference to sections 4.2 and 4.8). The severity of dermatological reactions often correlates with the clinical efficacy of the EGFR inhibitor. For patients who have not developed skin toxicity after 2-4 cycles of therapy, a reassessment of the treatment effect is recommended.
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. Data on the development of anti-panitumumab antibodies has been evaluated using two different screening immunoassays for the detection of binding anti-panitumumab antibodies (an ELISA which detects high-affinity antibodies, and a Biosensor Immunoassay which detects both high and low-affinity antibodies). For patients whose sera tested positive in either screening immunoassay, an in vitro biological assay was performed to detect neutralising antibodies.
As monotherapy:
• The incidence of binding antibodies (excluding predose and transient positive patients) was < 1% as detected by the acid-dissociation ELISA and 3.8% as detected by the Biacore assay;
• The incidence of neutralising antibodies (excluding predose and transient positive patients) was < 1%;
• Compared with patients who did not develop antibodies, no relationship between the presence of anti-panitumumab antibodies and pharmacokinetics, efficacy and safety has been observed.
In combination with irinotecan- or oxaliplatin-based chemotherapy:
• The incidence of binding antibodies (excluding predose positive patients) was 1.0% as detected by the acid-dissociation ELISA and < 1% as detected by the Biacore assay;
• The incidence of neutralising antibodies (excluding predose positive patients) was < 1%;
• No evidence of an altered safety profile was found in patients who tested positive for antibodies to Vectibix.
The detection of antibody formation is dependent on the sensitivity and specificity of the assay. The observed incidence of antibody positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease, therefore, comparison of the incidence of antibodies to other products may be misleading.
Clinical efficacy as monotherapy
The efficacy of Vectibix as monotherapy in patients with metastatic colorectal cancer (mCRC) who had disease progression during or after prior chemotherapy was studied in a randomised controlled trial (463 patients) and open-label, single-arm trials (384 patients).
A multinational, randomised, controlled trial was conducted in 463 patients with EGFR-expressing metastatic carcinoma of the colon or rectum after confirmed failure of oxaliplatin and irinotecan-containing regimens. Patients were randomised 1:1 to receive Vectibix at a dose of 6 mg/kg given once every two weeks plus best supportive care (not including chemotherapy) (BSC) or BSC alone. Patients were treated until disease progression or unacceptable toxicity occurred. Upon disease progression BSC alone patients were eligible to crossover to a companion study and receive Vectibix at a dose of 6 mg/kg given once every two weeks.
Of 463 patients, 63% were male. The median age was 62 years (range 27 to 83), and 99% were Caucasian. Three hundred and ninety-six (86%) patients had a baseline ECOG Performance Status of 0 or 1. Sixty-seven percent of patients had colon cancer and 33% had rectal cancer.
The primary endpoint was progression-free survival (PFS). In an analysis adjusting for potential bias from unscheduled assessments, the rate of disease progression or death in patients who received Vectibix was reduced by 40% relative to patients that received BSC [Hazard Ratio = 0.60, (95% CI 0.49, 0.74), stratified log-rank p < 0.0001]. There was no difference seen in median PFS times as more than 50% of patients progressed in both treatment groups before the first scheduled visit.
The study was retrospectively analysed by wild-type KRAS status versus mutant KRAS status. KRAS mutation status was determined by analysis of archived paraffin embedded tumour tissue.
Tumour samples obtained from the primary resection of colorectal cancer were analysed for the presence of the seven most common activating mutations in the codon 12 and 13 (Gly12Asp, Gly12Ala, Gly12Val, Gly12Ser, Gly12Arg, Gly12Cys, and Gly13Asp) of the KRAS gene by using an allele-specific polymerase chain reaction. 427 (92%) patients were evaluable for KRAS status of which 184 had mutations. In an analysis adjusting for potential bias from unscheduled assessments the hazard ratio for PFS was 0.49 (95% CI: 0.37-0.65) in favour of panitumumab in the wild-type KRAS group and 1.07 (95% CI: 0.77-1.48) in the KRAS mutant group. The difference in median PFS in the wild-type KRAS group was 8 weeks. The progression-free survival rates at the first scheduled visit (week 8) in the wild-type KRAS group were 59.7% on Vectibix plus BSC and 21.0% on BSC alone, a difference of 38.7% [95% CI: 27.4, 50.0]. The difference in median PFS in the mutant KRAS group was 0 weeks. The progression-free survival rates at the first scheduled visit (week 8) in the mutant KRAS group were 21.4% on Vectibix plus BSC and 28.0% on BSC alone, a difference of -6.6% [95% CI: -19.0, 5.9]. There were no differences in overall survival seen in either group. In the wild-type KRAS group the response rate was 17% for panitumumab and 0% for BSC. In the mutant KRAS group there were no responses in either treatment arm. Stable disease rates in the wild-type KRAS group were 34% for panitumumab and 12% for BSC. The stable disease rates in the mutant KRAS group were 12% for panitumumab and 8% for BSC. Response rate (investigator assessment) in patients that crossed over to panitumumab after progression on BSC alone was 22% (95% CI: 14.0, 31.9) for those with wild-type KRAS tumours and 0% (95% CI: 0.0, 4.3) for those with mutant KRAS tumours.
PFS – Patients with mutant and wild-type KRAS
Wild-Type KRAS
Unscheduled tumour assessments were moved to the nearest scheduled timepoint
Mutant KRAS
Unscheduled tumour assessments were moved to the nearest scheduled timepoint
Clinical efficacy in combination with chemotherapy
Summary of key final efficacy results in pivotal studies: Vectibix in combination with chemotherapy.
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