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

Vectibix®: Resources, readiness, and dermatologic toxicity risks

VECTIBIX® (PANITUMUMAB) DERMATOLOGIC TOXICITY

Pills and tablets

According to the Gorji et al. meta-analysis of 10 studies, oral antibiotics were the most efficacious prophylactic option for acneiform eruptions in EGFR inhibitors.2,*

12 days

12 DAYS FROM FIRST VECTIBIX® DOSE TO ONSET OF DERMATOLOGIC TOXICITY1

Median time to onset of dermatologic, nail, or ocular toxicity was reported in a study of 229 patients treated with Vectibix® monotherapy.

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)].

EGFR = epidermal growth factor receptor.

*Based on a meta-analysis of 10 randomized controlled trials (893 patients) from 2007 through 2016 evaluating the use of oral antibiotics for prevention and treatment of EGFR inhibitor-associated acneiform rash.

MASCC GUIDELINES: CONSIDERATIONS FOR ANTI-EGFR ASSOCIATED DERMATOLOGIC TOXICITIES3

Prophylactic measures are recommended by MASCC unless contraindicated based on patient and/or health care provider factors.3

Select information provided is an adaptation. Note that other information that may be relevant is included in the publication. Prescribers are advised to review the original source and entire article via the QR code provided below.

EGFR = epidermal growth factor receptor; MASCC = Multinational Association of Supportive Care in Cancer.

Prophylactic measures may help reduce the severity of dermatologic toxicities2

PROPHYLACTIC DERMATOLOGIC APPROACHES

MASCC recommends beginning prophylactic dermatologic measures at least 1 day prior to initiating anti-EGFR treatment3

Pills and tablets

ANTIBIOTICS

Use per prescribing information

Sunscreen

SUNSCREEN

Applied to exposed skin areas before going outdoors

Skin moisturizer

SKIN MOISTURIZER

Applied to face, hands, feet, neck, back, and chest daily in the morning and evening

Topical steroid

TOPICAL STEROID (eg, hydrocortisone cream)

Applied to face, hands, feet, neck, back, and chest daily in the morning and at bedtime

Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and protective clothing and limit sun exposure while receiving Vectibix®1

EGFR = epidermal growth factor receptor; MASCC = Multinational Association of Supportive Care in Cancer.

DOSE MODIFICATIONS1

INFUSION REACTIONS

  • Reduce infusion rate by 50% in patients experiencing a mild or moderate (grade 1 or 2) infusion reaction for the duration of that infusion
  • Terminate the infusion in patients experiencing severe infusion reactions. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix®

DERMATOLOGIC OR SOFT TISSUE TOXCITIES

  • Monitor patients who develop dermatologic or soft-tissue toxicities while receiving Vectibix® for the development of inflammatory or infectious sequelae

GRADE 3 Dermatologic Reaction*

Vectibix® (panitumumab) dose modications for grade 3 dermatologic reaction Vectibix® (panitumumab) dose modications for grade 3 dermatologic reaction

GRADE 4 Dermatologic Reaction*

Grade 4: Permanently discontinue Vectibix® (panitumumab)

*National Cancer Institute—Common Toxicity Criteria/Common Terminology Criteria for Adverse Events (NCI-CTC/CTCAE).

EXPLORE VIDEOS & PODCASTS

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 (NCI-CTC 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. Gorji M, Joseph J, Pavlakis N, Smith S. Asia-Pac J Clin Oncol. 2022;18:526-539. 3. Lacouture ME, Anadkat MJ, Bensadoun RJ, et al. Support Care Cancer. 2011;19:1079-1095. 4. Kobayashi Y, Komatsu Y, Yuki S, et al. Future Oncol. 2015;11:617-627.

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