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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CLINICAL GUIDELINES SUGGEST THAT PATIENTS WITH WT RAS* mCRC SHOULD RECEIVE TARGETED TREATMENT1,2

A RETROSPECTIVE REVIEW OF PATIENTS WITH METASTATIC COLON CANCER (mCC) DIAGNOSED BETWEEN 2013 AND 2017 SHOWED

BIOMARKER TESTING IN mCC PATIENTS HAS FALLEN SHORT OF GUIDELINE RECOMMENDATIONS2

GUIDELINE-ALIGNED BIOMARKER TESTING WAS COMPLETED IN 40% (601 OUT OF 1,497) OF PATIENTS IN THIS STUDY2,†

Patients were more likely to have guideline-aligned biomarker testing if they were treated at an academic center2

Biomarker testing recommendations vs. reality

A retrospective review of the COTA database was performed to identify patients with pathologically confirmed metastatic colon cancer (mCC) diagnosed between January 1, 2013 and December 1, 2017. A total of 1,497 patients with mCC were identified in the observational database. The study included patients with metastatic colon cancer and excluded rectal cancer cases. The COTA database included demographic, diagnostic, treatment, and quality-of-care information for patients with colon cancer abstracted from the electronic health records from 23 practices, including 258 oncologists in Arkansas, Maryland, Michigan, New Jersey, New York, and Tennessee.2

*Defined as wild type in both KRAS and NRAS.3

†Testing for a given biomarker was considered “guideline aligned” if the NCCN guidelines recommended testing for that biomarker for the entire year being analyzed. Guideline-aligned testing in 2013 and 2014 included testing for KRAS by any methodology, in 2015 included extended testing of NRAS and KRAS, and in 2016 and 2017 included extended testing of both KRAS and NRAS, BRAF testing by any methodology, and MSI/dMMR analysis by any methodology.2

COTA = clinically curated EHR data; dMMR = deficient mismatch repair; mCRC = metastatic colorectal cancer; MSI = micro-satellite instability; WT = wild-type.

ASCO RECOMMENDS ANTI-EGFR THERAPY FOR 1L LEFT-SIDED WT RASRAS* mCRC1

SYSTEMIC THERAPY FOR mCRC ALGORITHM4

Systemic therapy for metastatic colorectal cancer (mCRC) Algorithm

For full treatment guidelines see Morris VK, et al. J Clin Oncol. 2023;41:678-700.

*Defined as wild type in both KRAS and NRAS.3

†Decisions regarding treatment options and sequencing for all patients with mCRC should be made within the context of an MDT.

‡Doublet CT should be offered, or triplet CT may be offered. Shared decision-making is recommended, including a discussion of the potential for benefit and risk of harm; while survival and recurrence outcomes are improved, grade 3 or greater adverse events are more frequent with triplet CT compared to doublet CT.

§Anti-EGFR therapy is not recommended for patients with RAS-mutant mCRC.

**Anti-EGFR therapy is not recommended as a lone biologic agent for treatment-naïve patients with BRAF V600E-mutant mCRC.

††Although anti-EGFR therapy is preferred, anti-VEGF therapy remains an active treatment option for patients with left-sided treatment-naïve RAS wild-type mCRC.

This algorithm is derived from recommendations in Treatment of Metastatic Colorectal Cancer: ASCO Guideline. This is a tool based on an ASCO Guideline and is not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients. This tool does not purport to suggest any particular course of medical treatment. Use of the guideline and this tool are voluntary.

ASCO = American Society of Clinical Oncology; CT = chemotherapy; dMMR = deficient mismatch repair; doublet CT = FOLFOX, CAPOX, or FOLFIRI; EGFR = epidermal growth factor receptor; mCRC = metastatic colorectal cancer; MDT = multidisciplinary team; MSI = microsatellite instability; NCCN = National Comprehensive Cancer Network; triplet CT = FOLFOXIRI.

PARADIGM reinforces the value of:

  • Conducting early biomarker testing to determine a patient’s RAS status
  • Including tumor sidedness as a criterion for the selection of biologic therapies
  • Prescribing Vectibix® + FOLFOX as 1L therapy in newly diagnosed patients with WT RAS* and left-sided mCRC

SEE HOW VECTIBIX® PATIENTS WITH WT RAS* AND LEFT-SIDED PRIMARY TUMORS COMPARED TO AVASTIN® IN THE PARADIGM TRIAL 5

SEE PARADIGM RESULTS

LEARN HOW VECTIBIX® CLINICAL DATA HELPED EVOLVE BIOMARKER-BASED DECISIONS IN PATIENTS WITH mCRC

Vectibix® (panitumumab) podcast as experts discuss studies and recommendation treatments for patients with WT RAS mCRC

VECTIBIX® PODCAST: BIOMARKER ANALYSIS FOR THE TREATMENT OF NEWLY DIAGNOSED mCRC

With Dr. Philip Philip and Dr. Kurt Tauer

Biomarker Analysis for the Treatment of Newly Diagnosed …

Drs. Philip and Tauer are paid consultants for Amgen.

*Defined as wild type in both KRAS and NRAS.3

FOLFOX = fluorouracil, leucovorin, and oxaliplatin; OS = overall survival; PARADIGM = Panitumumab and RAS, Diagnostically useful Gene Mutation for metastatic colorectal cancer (mCRC); WT = wild type.

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REVIEW CLINICAL DATA

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. Morris VK, Kennedy EB, Baxter NN, et al. J Clin Oncol. 2023;41:678-700. 2. Gutierrez M, Price K, Lanman R, et al. JCO Precis Oncol. 2019;3:PO.19.00274. 3. Vectibix® (panitumumab) prescribing information, Amgen. 4. Systemic therapy for metastatic colorectal cancer (mCRC) algorithm. ASCO Guidelines®. 2022. 5. Watanabe J, Muro K, Shitara K, et al. JAMA. 2023;329:1271-1282.

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