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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20100007 study

PROSPECTIVE EVALUATION OF
PATIENTS WITH CHEMOREFRACTORY
WT RAS* mCRC1

A phase 3, open-label, multicenter, randomized (1:1) study of 377 patients with chemorefractory WT KRAS† mCRC treated with Vectibix® Q2W + BSC or BSC alone. Eligible patients were required to have received prior therapy with irinotecan, oxaliplatin, and a thymidylate synthase inhibitor.1,2

  • The primary endpoint was OS in patients with WT KRAS (exon 2 in codons 12 and 13)1,2
  • RAS tumor mutation status was available for 86% of patients: 270 (72%) patients had WT RAS tumors, 54 (14%) had mutant RAS tumors, and 54 (14%) had unknown RAS tumor status1

Prespecified key secondary endpoints:1

  • OS, PFS, and ORR§ in patients with WT RAS mCRC

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

†Exon 2 in codons 12 and 13.1

‡RAS mutation status was determined for 324 patients using Sanger bidirectional sequencing.2

§Response was evaluated by investigators per RECIST version 1.1 criteria.2

BSC = best supportive care; ECOG PS = Eastern Cooperative Oncology Group Performance Status; mCRC = metastatic colorectal cancer; ORR = objective response rate; OS = overall survival; PFS = progression-free survival; Q2W = every 2 weeks; RECIST = Response Evaluation Criteria in Solid Tumors; WT = wild type.

44.9% INCREASE (3.1-MONTH ABSOLUTE DIFFERENCE) IN MEDIAN OS WITH VECTIBIX® + BSC VS BSC ALONE1

SIGNIFICANT IMPROVEMENT IN OS WITH
VECTIBIX® + BSC IN PATIENTS WITH WT RAS* mCRC (P = 0.0135)1

WT RAS mCRC population
(n = 270)		 Vectibix® + BSC
(n = 142)		 BSC alone
(n = 128)
OS median months (95% CI) 10.0
(8.7-11.6)		 6.9
(5.2-7.9)
HR (95% CI), P value 0.70 (0.53-0.93) P = 0.0135
PFS median months (95% CI) 5.2
(3.5-5.3)		 1.7
(1.6-2.2)
HR (95% CI), P value 0.46 (0.35-0.59) P < 0.0001
ORR† (95% CI) 31%
(23.5%-39.3%)		 2.3
(0.5%-6.7%)
Data table for overall survival with Vectibix® (panitumumab) + BSC vs BSC alone

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

†Response was evaluated by investigators per RECIST version 1.12

BSC = best supportive care; CI = confidence interval; HR = hazard ratio; mCRC = metastatic colorectal cancer; ORR = objective response rate; OS = overall survival; PFS = progression-free survival; RECIST = Response Evaluation Criteria in Solid Tumors; WT = wild type.

CHEMOREFRACTORY HYPOTHETICAL
PATIENT PROFILE

Hypothetical newly diagnosed chemorefractory patient, Connie, who is a 68 year old woman
Hypothetical newly diagnosed chemorefractory patient, Connie, who is a 68 year old woman

CHEMOREFRACTORY

Name
Connie*
Gender
Female
Age
68
Occupation
Salesperson

*A hypothetical patient profile of treatment for a chemorefractive mCRC patient.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; CBC = complete blood count; CT = computed tomography; ECOG PS = Eastern Cooperative Oncology Group Performance Status; FOLFIRI = leucovorin calcium (folinic acid), fluorouracil, and irinotecan hydrochloride; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; Hb = hemoglobin; mCRC = metastatic colorectal cancer; PLT = platelet; WBC = white blood count; WT = wild type.

What clinical characteristics affect your treatment decision for chemorefractory mCRC?

Medical history

  • Osteoarthritis

Presentation

  • Initial presentation of mild abdominal discomfort and mild anemia
  • Colonoscopy revealed a non-obstructing mass in the left colon
  • CT scan revealed liver and lung metastases that were unresectable

Prior therapy

  • Newly diagnosed treatment: FOLFOX + Avastin®
    • Progressed on therapy after 9 months
  • Second-line treatment: FOLFIRI + Avastin®
    • Progressed on therapy after 7 months with liver and lung metastases

Performance status

  • ECOG PS = 1

Laboratory results

  • ALT: 135 U/L; AST: 250 U/L
  • CBC
    • WBC: 4.0 x 103 mL/µL
    • Neutrophil: 1.6 x 103 mL/µL
    • Hb: 9.0 g/dL
    • PLT: 125 x 103 mL/µL
  • Bilirubin: 1.8 mg/dL

RAS status

  • WT RAS (WT in both KRAS and NRAS)

Imaging results

  • CT scan indicated diffuse metastatic involvement of lung and liver

Surgery consult on metastatic disease

  • Unresectable due to number of metastatic sites

*A hypothetical patient profile of treatment for a chemorefractive mCRC patient.

ALT = alanine aminotransferase; AST = aspartate aminotransferase; ASPECCT = A Study of Panitumumab efficacy and safety Compared to Cetuximab; CBC = complete blood count; CT = computed tomography; ECOG PS = Eastern Cooperative Oncology Group Performance Status; FOLFIRI = leucovorin calcium (folinic acid), fluorouracil, and irinotecan hydrochloride; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; Hb = hemoglobin; mCRC = metastatic colorectal cancer; PLT = platelet; WBC = white blood count; WT = wild type.

EXPLORE ASPECCT STUDY

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. Kim TW, Elme A, Kusic Z, et al. Br J Cancer. 2016;115:1206-1214.

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