INDICATION AND LIMITATION OF USE

Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):Read More

Prescribing Information Indication Important Safety Information Patient Site
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PRIME study

TARGETED 1L THERAPY WITH VECTIBIX®
INCREASED SURVIVAL FOR NEWLY DIAGNOSED
WT RAS* mCRC PATIENTS1,2

PRIME: A phase 3, open-label, randomized (1:1), multicenter study of Vectibix® Q2W + FOLFOX4 vs FOLFOX4 Q2W alone in newly diagnosed patients with mCRC1,2

PRIME: A phase 3 (1:1) randomized study of Vectibix Q2W + FOLFOX4 VS FOLFOX4 Q2W alone
PRIME: A phase 3 (1:1) randomized study of Vectibix Q2W + FOLFOX4 VS FOLFOX4 Q2W alone
  • Patients with mutant RAS tumors should not be treated with Vectibix®1
  • Of the 656 patients with WT KRAS exon 2 mCRC, 620 patients were assessed for RAS mutation status, of which 17% harbored mutations in KRAS exons 3 and 4 or in NRAS exons 2, 3, and 4. Post-hoc analyses of PFS, OS‡, and ORR§ were conducted in 512 patients with WT RAS1

*Defined as wild type in both KRAS and NRAS.1

†Exon 2 in codons 12 and 13.1

‡OS with updated information based on events in 82% of patients.1

§Objective tumor response was evaluated by blinded central radiology review using modified RECIST criteria.3

FOLFOX = fluorouracil, leucovorin, and oxaliplatin; MT = mutant type; mCRC = metastatic colorectal cancer; ORR = objective response rate; OS = overall survival; PFS = progression-free survival; PRIME = Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; Q2W = every 2 weeks; RECIST = Response Evaluation Criteria in Solid Tumors; WT = wild type.

In the post hoc analysis of PATIENTS WITH WT RAS* mCRC from PRIME1

Patient demographics
and clinical
characteristics1

Demographic or clinical characteristic WT RAS* mCRC
Male 65%
Race
  • White
  • Black
  • Hispanic or Latino
  •  
  • 91%
  • 2%
  • 5%
Colon cancer 65%
Rectal cancer 35%
ECOG PS
  • 0
  • 1
  • 2
  •  
  • 57%
  • 37%
  • 6%
Median age, years 61

*Defined as wild type in both KRAS and NRAS.1

ECOG PS = Eastern Cooperative Oncology Group Performance Status; mCRC = metastatic colorectal cancer; PRIME = Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; WT = wild type.

In the PRIME study1

27.8% improvement in median PFS with
Vectibix® + FOLFOX4 vs
FOLFOX4 alone1

Post hoc analysis in the mCRC
WT RAS* subgroup in PRIME1

  • There are no OS or PFS benefits in patients with RAS-mutant mCRC treated with Vectibix®1

*Defined as wild type in both KRAS and NRAS.1

CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; mCRC = metastatic colorectal cancer; OS = overall survival; PFS = progression-free survival; PRIME = Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; WT = wild type.

In the post-hoc analysis
of the PRIME study

Vectibix® + FOLFOX4
improved ORR* vs
FOLFOX4 alone1

ORR in patients with WT RAS† mCRC

ORR in patients with WT RAS† mCRC in the PRIME study

*Objective tumor response was evaluated by blinded central radiology review using modified RECIST criteria.3

†Defined as wild type in both KRAS and NRAS.1

CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; mCRC = metastatic colorectal cancer; ORR = objective response rate; PRIME = Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; RECIST = Response Evaluation Criteria in Solid Tumors; WT = wild type.

IN THE POST HOC ANALYSIS
OF THE PRIME STUDY

5.6-month increase
in median OS1,*

PRIME study 5.6 month increase in median OS graph
  • There are no OS or PFS benefits in patients with RAS-mutant mCRC treated with Vectibix®1

*OS with updated information based on events in 82% of patients.1

CI = confidence interval; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; HR = hazard ratio; mCRC = metastatic colorectal cancer; OS = overall survival; PFS = progression-free survival; PRIME = Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer To Determine Efficacy; WT = wild type.

In the phase 3 PRIME study

Safety profile in
patients with
WT KRAS* mCRC1

The safety profile in patients with
WT RAS† was similar to that of
patients with WT KRAS mCRC

Adverse reactions (≥ 5% difference) observed in patients with WT KRAS tumors treated with Vectibix® + FOLFOX4 compared to FOLFOX4 alone1,‡ Vectibix® + FOLFOX4
(n = 322) 		FOLFOX4 alone
(n = 327)
SYSTEM ORGAN CLASS
Preferred term
 Any
grade
n (%)		 Grade
3-4
n (%)		 Any
grade
n (%)		 Grade
3-4
n (%)
EYE DISORDERS
Conjunctivitis 58
(18%) 		5
(2%) 		10
(3%) 		—
GASTROINTESTINAL DISORDERS
Diarrhea 201
(62%) 		59
(18%) 		169
(52%) 		29
(9%)
Stomatitis 87
(27%) 		15
(5%) 		42
(13%) 		1
(< 1%)
GENERAL DISORDER AND
ADMINISTRATION-SITE CONDITIONS
Mucosal inflammation 82
(25%) 		14
(4%) 		53
(16%) 		1
(< 1%)
Asthenia 79
(25%) 		16
(5%) 		62
(19%) 		11
(3%)
INFECTIONS AND INFESTATIONS
Paronychia 68
(21%) 		11
(3%) 		— — 
INVESTIGATIONS
Weight decreased 58
(18%) 		3
(< 1%) 		22
(7%) 		—
METABOLISM AND NUTRITION DISORDERS
Anorexia 116
(36%) 		14
(4%) 		85
(26) 		6
(2%)
Hypomagnesemia 96
(30%) 		21
(7%) 		26
(8%) 		1
(< 1%)
Hypokalemia 68
(21%) 		32
(10%) 		42
(13%) 		15
(5%)
Dehydration 26
(8%) 		8
(2%) 		10
(3%) 		5
(2%)
RESPIRATORY, THORACIC, AND
MEDIASTINAL DISORDERS
Epistaxis 46
(14%) 		— 30
(9%) 		—
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Rash 179
(56%) 		55
(17%) 		24
(7%) 		1
(< 1%)
Acneiform dermatitis 104
(32%) 		33
(10%) 		— —
Pruritus 75
(23%) 		3
(< 1%) 		14
(4%) 		—
Dry skin 68
(21%) 		5
(2%) 		13
(4%) 		—
Erythema 50
(16%) 		7
(2%) 		14
(4%) 		—
Skin fissures 50
(16%) 		1 (< 1%) 1 (< 1%) —
Alopecia 47
(15%) 		— 30
(9%) 		—
Acne 44
(14%) 		10
(3%) 		1 (< 1%) —
Nail disorder 32
(10%) 		4
(1%) 		4
(1%) 		—
Palmar-plantar erythrodysesthesia syndrome 30
(9%) 		4
(1%) 		9
(3%) 		2
(< 1%)
Safety Profile in patients with WT KRAS* mCRC
  • Adverse reactions that did not meet the threshold criteria for inclusion in this table were flushing (3% vs < 1%), abdominal pain (28% vs 23%), localized infection (3.7% vs < 1%), cellulitis (2.5% vs 0%), hypocalcemia (5.6% vs 2.1%), and deep vein thrombosis (5.3% vs 3.1%)1
Selected chemotherapy-associated adverse reactions2,4,‡ Vectibix® + FOLFOX4
(n = 322) 		FOLFOX4 alone
(n = 327)
SYSTEM ORGAN CLASS
Preferred term
 Any
grade
n (%)		 Grade
3-4
n (%)		 Any
grade
n (%)		 Grade
3-4
n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Neutropenia 194
(60%)		 133
(41%)		 202
(62%)		 132
(40%)
Thrombocytopenia 62
(19%)		 12
(4%)		 88
(27%)		 15
(5%)
Anemia 49
(15%)		 14
(4%)		 43
(13%)		 9
(3%)
GASTROINTESTINAL DISORDERS
Nausea 145
(45%)		 16
(5%)		 165
(50%)		 3
(1%)
Vomiting 98
(30%)		 11
(3%)		 105
(32%)		 9
(3%)
Constipation 93
(29%)		 5
(2%)		 91
(28%)		 2
(1%)
GENERAL DISORDER AND
ADMINISTRATION-SITE CONDITIONS
Pyrexia (fever) 100
(31%) 		2
(1%) 		93
(28%) 		7
(2%)
Fatigue 119
(37%) 		31
(10%) 		112
(34%) 		10
(3%)
NERVOUS SYSTEM DISORDERS
Peripheral neuropathy 61
(19%) 		18
(6%) 		80
(24%) 		18
(5%)
Peripheral sensory neuropathy 47
(15%) 		5
(2%) 		53
(16%) 		6
(2%)
Paresthesia 107
(33%) 		28
(9%) 		110
(34%) 		21
(6%)
PSYCHIATRIC DISORDERS
Insomnia 43
(13%) 		1
(< 1%) 		51
(16%) 		1
(< 1%)
Selected chemotherapy-associated adverse reactions data

*Exon 2 in codons 12 and 13.1

†Defined as wild type in both KRAS and NRAS.1

‡Of the 656 patients in the PRIME study with WT KRAS mCRC, 649 were evaluated for safety.1

FOLFOX = fluorouracil, leucovorin, and oxaliplatin; mCRC = metastatic colorectal cancer; PRIME = Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy; WT = wild type.

PRIME HYPOTHETICAL PATIENT PROFILES

Hypothetical newly diagonosed patient profile for Roy, a 64 year old male
Hypothetical newly diagonosed patient profile for Roy, a 64 year old male

NEWLY
DIAGNOSED,
LIVER-LIMITED

Name
Roy*
Gender
Male
Age
64
Occupation
Middle-school teacher
Right lobe and left lobe of liver

What clinical characteristics affect your treatment decision for newly diagnosed mCRC?

Medical history

  • Mild hyperlipidemia, controlled on statin therapy

Presentation

  • 3-month history of worsening constipation, bloating, and blood in stool
  • Colonoscopy confirmed 4-cm, non-obstructing mass in the left colon

Pathology report

  • Moderately differentiated adenocarcinoma

Performance status

  • ECOG PS = 1

Laboratory results

  • ALT: 70 U/L; AST: 180 U/L
  • CBC: Moderate anemia (Hb: 9.2 g/dL)

RAS status

  • WT RAS (WT in both KRAS and NRAS)

Imaging results

  • CT scan indicated liver-limited metastases: 2 bilobar lesions (right: 3.45 cm; left: 6.54 cm)

Surgery consult on metastatic disease

  • Potentially resectable metastases
  • Surgeon feels metastatic disease is potentially resectable—treatment goal is to downgrade the tumor

Images are shown for illustrative purposes only

*A hypothetical patient profile of treatment for a newly diagnosed mCRC patient.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; CT = computed tomography; ECOG PS = Eastern Cooperative Oncology Group Performance Status; Hb = hemoglobin; mCRC = metastatic colorectal cancer; WT = wild type.

Hypothetical newly diagnosed patient profile for Brian, a 62 year old male
Hypothetical newly diagnosed patient profile for Brian, a 62 year old male

NEWLY
DIAGNOSED

Name
Brian*
Gender
Male
Age
62
Occupation
Auto mechanic
Right and left sides of lung and liver

What clinical characteristics affect your treatment decision for newly diagnosed mCRC?

Medical history

  • Mild GERD

Presentation

  • Sought medical treatment for frequent episodes of moderate/severe right upper quadrant pain
  • Also complains of shortness of breath and pleuritic pain; pain has noticeably worsened over the last month
  • Taking frequent pain medication
  • Colonoscopy indicated a 5-cm non-obstructing mass in the sigmoid colon

Pathology report

  • Moderately differentiated adenocarcinoma

Performance status

  • ECOG PS = 1

Laboratory results

  • ALT: 100 U/L; AST: 210 U/L
  • CBC: Mild/moderate anemia (Hb: 9.8 g/dL)
  • Bilirubin: 1.8 mg/dL

RAS status

  • WT RAS (WT in both KRAS and NRAS)

Imaging results

  • CT scan indicated diffuse, bulky metastatic involvement of lung and liver

Surgery consult on metastatic disease

  • Unresectable due to number of metastatic sites

Images are shown for illustrative purposes only

*A hypothetical patient profile of treatment for a newly diagnosed mCRC patient.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; CT = computed tomography; ECOG PS = Eastern Cooperative Oncology Group Performance Status; GERD = gastroesophageal reflux disease; Hb = hemoglobin; mCRC = metastatic colorectal cancer; WT = wild type.

EXPLORE PARADIGM STUDY

Dr. Marwan Fakih’s perspective on Vectibix® as a treatment option for newly diagnosed WT RAS mCRC

FROM PRIME TO PRACTICE

Learn Dr. Marwan Fakih’s perspective on Vectibix® as a treatment option for newly diagnosed WT RAS* mCRC.

WATCH NOW

Dr. Fakih is a paid consultant for Amgen.

*WT in both KRAS and NRAS.1

mCRC = metastatic colorectal cancer; WT = wild type.

Dr. Fakih is a paid consultant for Amgen.

IMPORTANT SAFETY INFORMATION

BOXED WARNING:
DERMATOLOGIC TOXICITY

Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix® monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

  • In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI0CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix®. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures.
  • Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix®. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix®. 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 Vectibix® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix® concerning dermatologic toxicity are provided in the product labeling.
  • Vectibix® is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as “RAS.”
  • Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix® and FOLFOX versus FOLFOX alone.
  • Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix® treatment, periodically during Vectibix® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.
  • In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grades 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.
  • Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix® in combination with chemotherapy.
  • Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix®. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix® therapy. Discontinue Vectibix® therapy if ILD is confirmed.
  • In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix® versus the risk of pulmonary complications must be carefully considered.
  • Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix®.
  • Serious cases of keratitis, ulcerative keratitis, and corneal perforation have occurred with Vectibix® use. Monitor for evidence of keratitis, ulcerative keratitis, or corneal perforation. Interrupt or discontinue Vectibix® therapy for acute or worsening keratitis, ulcerative keratitis, or corneal perforation.
  • In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0).
  • NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix®-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix®-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix®, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy.
  • Vectibix® can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix®.
  • In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
  • The most commonly reported adverse reactions (≥ 20%) with Vectibix® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration.

Please see Vectibix® full Prescribing Information, including Boxed WARNING.

INDICATION

Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC):

  • As first-line therapy in combination with FOLFOX.
  • As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

LIMITATION OF USE

Vectibix® is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.

IMPORTANT SAFETY INFORMATION

BOXED WARNING:
DERMATOLOGIC TOXICITY

Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix® monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

References 1. Vectibix® (panitumumab) prescribing information, Amgen. 2. Douillard J-Y, Oliner KS, Siena S, et al. N Engl J Med. 2013;369:1023-1034. 3. Douillard J-Y, Oliner KS, Siena S, et al. J Clin Oncol. 2010;28:4697-4705. 4. Data on File, Amgen, 2012.

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