Vectibix® (panitumumab) for Wild-Type RAS mCRC | HCP_Internet

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® 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, and 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. Visit Patient Site Prescribing Information Indication Important Safety Information Visit Patient Site RASStory KRAS andNRAS WTRAS identification Listen to experts discuss extended RAS testing Newly Diagnosed Data PRIME study PRIME study design Progression-free survival Objective response rate Overall survival Safety profile An expert discusses the importance of Vectibix® as a treatment for newly diagnosed mCRC Hear experts discuss the real-world implications of the PRIME study ChemorefractoryDataData 20100007 study ASPECCT study Review a hypothetical patient profile for chemorefractory mCRC Administration Hypothetical Patient Profiles Newly diagnosed, liver-limited: Roy Newly diagnosed: Brian Chemorefractory: Connie Learn how WT RASmCRC patients were identified in PRIME Access VECTIBIX® (panitumumab) LEAPS AHEAD in patients with WT RAS* mCRC1 5.6-month increase in median OS† with Vectibix® + FOLFOX vs FOLFOX alone1 5.6-month increase in medianOS†with Vectibix® + FOLFOX vs FOLFOXalone1PRIME (Vectibix® + FOLFOX vs FOLFOX alone): N = 1,183,randomized (1:1), phase 3, open-label, multicenter study of mCRC. In this post-hoc analysis,patients with WT RAS mCRC (n = 512) were evaluated.1,2 Median OS (WT RAS mCRC): 25.8 vs 20.2 months; HR = 0.77 (95% CI: 0.64–0.94)1Explore data in newly diagnosed mCRC with WT RASThe NCCN Clinical Practice Guidelines in Oncology (NCCNGuidelines®) for Colon Cancer and Rectal Cancer recommend panitumumab(VECTIBIX®) + FOLFOX as a first-line treatment option for certainpatients‡ with WT RAS mCRC3,4§ × Your browser does not support the audio element. × Your browser does not support the audio element. × Your browser does not support the audio element. Dr. Fakih is a paid consultant for Amgen. Drs. Fakih, Philip, Tauer, de Zarraga, and al‑Rajabi are paid consultants for Amgen. From PRIME to Practice Join Dr. Marwan Fakih as he shares his perspective on Vectibix® as a treatment option for newly diagnosed WT RAS mCRC Watch Now Vectibix® podcast series In collaboration with ReachMD. Real-world treatment implications from the PRIMEstudy With Dr. Philip Philip and Dr. Kurt Tauer Listen Now Vectibix® and the evolution of biomarker‑based treatment in mCRC With Dr. Philip Philip and Dr. Kurt Tauer Listen Now Exploring an evidence-based treatment pathway for chemorefractory WTRAS mCRC With Dr. Fernando de Zarraga and Dr. Raed Al‑Rajabi Listen Now The importance of biomarker identification:See why testing for WT RAS is recommended1Learn more aboutWT RAS*Defined as wild type in both KRAS andNRAS.1†OS with updated information basedon events in 82% of patients.1‡See the guidelinesonline at NCCN.org for the full recommendation.§NCCN makes nowarranties of any kind whatsoever regarding their content, use or application and disclaims anyresponsibility for theirapplications or use in any way.CI =confidence interval; HR = hazard ratio; FOLFOX = fluorouracil, leucovorin, and oxaliplatin; mCRC =metastatic colorectal cancer;NCCN = National Comprehensive CancerNetwork; OS=overall survival; PRIME = Panitumumab Randomized Trial in Combination WithChemotherapy for Metastatic Colorectal Cancer to Determine Efficacy;WT = wild type.Learn about theimportance of identifying WT RAS CLOSE 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 grade 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 WARNINGBoxed WARNING. IndicationIndication 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 UseLimitation of Use Vectibix® is not indicated for the treatment of patients with RAS‑mutant mCRC or for whom RAS mutation status is unknown. SEE MORE IMPORTANT SAFETY INFORMATIONBOXED 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, References: Vectibix® (panitumumab) prescribing information, Amgen. Douillard J-Y, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010;28(31):4697-4705. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed September19,2018. To view the most recent and complete version of the guideline, go to NCCN.org. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.3.2018. ©National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed September19,2018. To view the most recent and complete version of the guideline, go to NCCN.org. 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