Amgen Announces KRAS Safety Update to U.S. Prescribing Information for Vectibix(R) (Panitumumab)
Class Labeling Recognizes KRAS as a Predictive Biomarker for anti-EGFr Antibody Monotherapy in Metastatic Colorectal Cancer Results from First Pivotal Trials Prospectively Evaluating KRAS Utility in Combination Therapy Expected In Third Quarter 2009
THOUSAND OAKS, Calif., July 17 /PRNewswire-FirstCall/ -- Amgen Inc. (Nasdaq: AMGN) today announced the U.S. Food and Drug Administration (FDA) has approved revisions to the U.S. prescribing information for the epidermal growth factor receptor (EGFr) class of antibodies, including Vectibix (panitumumab). This decision follows the FDA's December 2008 Oncologics Drugs Advisory Committee (ODAC) meeting where the clinical utility of the KRAS gene as a predictive biomarker in patients with metastatic colorectal cancer (mCRC) treated with anti-EGFr antibody was discussed.
"We are pleased that the FDA has recognized the clinical importance of KRAS as a predictive biomarker for anti-EGFr antibody therapy," said Sean Harper, M.D., chief medical officer and head of Global Development at Amgen.
The INDICATION AND USAGE section of the prescribing information has been updated to include that retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix is not recommended for the treatment of colorectal cancer with these mutations.
The CLINICAL STUDIES section of the prescribing information has been updated to reflect results from retrospective analyses across seven randomized clinical trials with agents in this class. This includes the first Phase 3 analysis that showed mCRC patients with mutated KRAS tumors do not respond to monotherapy with an EGFr-inhibiting antibody (the Vectibix "408" trial).
"With this label update, physicians can now eliminate anti-EGFr antibodies as a treatment option for patients with mutated KRAS tumors and redirect those patients to alternative therapies, avoiding unnecessary treatments in patients who are unlikely to benefit," said Sean Harper.
This label update is specific to the utility of KRAS as a biomarker for Vectibix used as a monotherapy. In the combination chemotherapy setting, the Vectibix "181" and "PRIME (203)" trials will be the first prospective Phase 3 clinical studies testing the clinical utility of KRAS as a predictive biomarker in mCRC patients in earlier lines of therapy. Data from the "181" and "PRIME (203)" trials are expected in the third quarter of 2009.
This update follows recent KRAS related action from key cancer organizations, including the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). A Clinical Provisional Opinion (CPO) was issued by ASCO in January, where the organization recommended the use of the KRAS biomarker in selecting the appropriate patients for anti-EGFr antibody therapy. In November 2008, the NCCN announced updates to their Guidelines on Colon and Rectal Cancers. The guideline updates included the recommendation that a determination of the KRAS gene status of either the primary tumor or a site of metastasis should be part of the pre-treatment work-up for patients diagnosed with metastatic colorectal cancer.
About Colorectal Cancer
Colorectal cancer is the third most common cancer diagnosed in men and in women in the United States (U.S.). The American Cancer Society estimates that about 106,100 new cases of colon cancer and 40,870 new cases of rectal cancer will be diagnosed in 2009. Colorectal cancer is the second leading cause of cancer death among men and women in the U.S. and it has been estimated that more than 49,000 people will die from colorectal cancer in 2009. That means that one person in the U.S. dies of colorectal cancer every 9.3 minutes.
Vectibix is indicated as a single agent for the treatment of patients with epidermal growth factor receptor (EGFr)- expressing metastatic colorectal carcinoma after disease progression on, or following fluoropyrimidine-, oxaliplatin- and irinotecan-containing chemotherapy regimens. The effectiveness of Vectibix as a single agent for the treatment of EGFr-expressing, metastatic colorectal carcinoma is based on progression-free survival. Currently no data demonstrate an improvement in disease-related symptoms or increased survival with Vectibix.
Important Product Safety Information
Dermatologic Toxicity: Dermatologic toxicities occurred in 89 percent of patients and were severe (NCI-CTC grade 3 and higher) in 12 percent of patients receiving Vectibix monotherapy. Withhold Vectibix for dermatologic toxicities that are grade 3 or higher or are considered intolerable. If toxicity does not improve to less than or equal to grade 2 within 1 month, permanently discontinue Vectibix. The clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage were reported.
Infusion Reactions: Severe infusion reactions occurred in approximately 1 percent of patients. Severe infusion reactions included anaphylactic reactions, bronchospasm, and hypotension. Although not reported with Vectibix, fatal infusion reactions have occurred with other monoclonal antibody products. Stop infusion if a severe infusion reaction occurs. Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix.
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