Printer Friendly

Vectibix(R) in Combination With Chemotherapy Significantly Improves Progression-Free Survival in First-Line Metastatic Colorectal Cancer.

THOUSAND OAKS, California Thousand Oaks, commonly referred to as "T.O." by residents, is a city in southeastern Ventura County, California, in the United States. It was named after the many oak trees that grace the area, and the city seal is adorned with an oak. , September 24 /PRNewswire/ --

Amgen (Nasdaq: AMGN) today announced detailed results from the Phase 3 '203' trial evaluating Vectibix(R) (panitumumab) administered in combination with FOLFOX FOLFOX 5-Fluorouracil, Leucovorin and Oxaliplatin (chemo treatment)  (an oxaliplatin-based chemotherapy) as the first-line treatment of metastatic Metastatic
The term used to describe a secondary cancer, or one that has spread from one area of the body to another.

Mentioned in: Coagulation Disorders


metastatic

pertaining to or of the nature of a metastasis.
 colorectal cancer (mCRC). In this trial, Vectibix significantly improved median progression-free survival (PFS PFS,
n post facilitation stretch; therapeutic approach utilized during proprioceptive neuromuscular facilitation in which the patient begins the stretch midway between the fully relaxed and fully stretched position and uses maximum level of effort to
) by 1.6 months (9.6 versus 8.0 months for patients treated with FOLFOX alone, (hazard ratio 0.80; p=0.02)) in patients with KRAS KRAS Knowledge Representation for Autonomous Systems  wild-type mCRC (primary endpoint). The results were presented at the 2009 ECCO An earlier Windows PIM from NetManage, Inc., Cupertino, CA (www.netmanage.com). ECCO provided a phone book, calendar, to-do list, outlining and notetaking. It was noted for its tightly integrated and sophisticated functions.  15 - ESMO ESMO European Society for Medical Oncology
ESMO European Student Moon Orbiter
ESMO Earth Science Mission Operations
ESMO Excited-State Molecular Orbital
 34 European Multidisciplinary Congress in Berlin, Germany (Abstract Number 10LBA (Logical Block Addressing) A method used to address hard disks by a single sector number rather than by cylinder, head and sector (CHS). LBA was introduced to support ATA/IDE drives as they reached 504MB, and Enhanced BIOSs in the PC translated CHS addressing into LBA ).

Further, the addition of Vectibix to chemotherapy also improved response rate in the KRAS wild-type patient population as measured by blinded central review (55 percent versus 48 percent in the FOLFOX only arm).

"I am very pleased with the outcome of this high quality trial which demonstrated that Vectibix improved progression-free survival and appeared to be well tolerated as a first-line metastatic colorectal cancer treatment in a selected patient population," said Jean-Yves Douillard, director Clinical and Translational Research, Medical Oncology Branch, Centre R Gauducheau, France and the study's principal investigator. "This is the first prospective Phase 3 data to demonstrate the importance of KRAS mutation as a predictive biomarker for Vectibix treatment in the first-line setting, providing definitive support for the use of the KRAS biomarker for selection of patients eligible for anti-EGFR therapy."

Importantly, in patients with tumors harboring activating KRAS mutations, PFS was significantly inferior in the Vectibix arm. For patients with mutant KRAS tumors, median PFS was 7.3 months with Vectibix in combination with FOLFOX vs. 8.8 months with FOLFOX alone (hazard ratio 1.29, p=0.02). These data confirm previous findings when oxaliplatin-based chemotherapy and an anti-epidermal growth factor receptor A growth factor receptor is a receptor which binds to growth factor. External links
  • MeSH Growth+Factor+Receptors


    
 (EGFR EGFR Epidermal Growth Factor Receptor (a kinase enzyme)
EGFR Estimated Glomerular Filtration Rate
) antibody are combined in patients bearing tumors with activating KRAS mutations.

Consistent with the PFS data, an interim analysis of overall survival, a secondary endpoint, demonstrated a reduction in overall survival in patients with KRAS mutant tumors receiving Vectibix. The median overall survival for patients with KRAS wild-type mCRC has not yet been reached. Long-term follow-up for survival continues and the primary analysis is expected in the fourth quarter of 2009.

Adverse event rates were comparable across arms with the exception of known toxicities associated with anti-epidermal growth factor receptor (EGFR) therapy such as rash, diarrhea and hypomagnesemia. Vectibix-related grade 3 infusion reactions were reported for two patients (less than 1 percent).

Originally designed to compare the treatment effect in the overall population, the study was amended to analyze outcomes with respect to the presence or absence of activating mutations in KRAS in the tumor itself. Tumor KRAS status was ascertained in 93 percent of the 1,183 patients enrolled in the trial, the highest percentage ever reported. Tumor KRAS tests were finalized after the completion of enrollment and prior to the primary analysis.

Earlier this week, data were presented from the '181' trial which showed that Vectibix administered in combination with FOLFIRI FOLFIRI Folinic Acid, Fluorouracil & Irinotecan (chemo treatment)  (an irinotecan-based chemotherapy) prolonged PFS by 2 months in patients with KRAS wild-type mCRC, compared to treatment with FOLFIRI alone (Abstract Number 14LBA).

Webcast Information

An analyst/investor event will also be held from the Congress on September 24th, at 6:30 a.m. Eastern Time to discuss data presented at ECCO-ESMO. A webcast of the event can be found on Amgen's Web site at www.amgen.com, under Investors. The audio webcast will be archived and available for replay for at least 72 hours.

Study Design

Patients enrolled in the '203' or PRIME trial (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) were randomized to receive either 6.0 mg/kg of Vectibix and FOLFOX4 once every two weeks (Q2W) or FOLFOX4 alone Q2W. The primary endpoint of the study is progression-free survival by KRAS status and secondary endpoints include overall survival, objective response rate, time to progression, duration of response and safety. Long-term follow up for overall survival is ongoing.

About KRAS

Results from studies performed over the last twenty-five years indicate that KRAS plays an important role in cell growth regulation. In mCRC, EGFR transmits signals through a set of intracellular proteins. Upon reaching the nucleus, these signals instruct the cancer cell to reproduce and metastasize me·tas·ta·size
v.
To be transmitted or transferred by or as if by metastasis.


Metastasize
Spread of cells from the original site of the cancer to other parts of the body where secondary tumors are formed.
, leading to cancer progression. Anti-EGFR antibody therapies work by blocking the activation of EGFR, thereby inhibiting downstream events that lead to malignant signaling. However, it is hypothesized that in patients whose tumors harbor a mutated KRAS gene, the KRAS protein is always turned "on," regardless of whether the EGFR has been activated or therapeutically inhibited. KRAS mutations occur in approximately 40-50 percent of mCRC.

About Colorectal Cancer

Colorectal cancer is the fourth most common cancer in men and the third most common cancer in women worldwide. In 2007, approximately 1.2 million cases of colorectal cancer were expected to occur globally. With more than 630,000 deaths worldwide per year, it is the second leading cause of cancer-related death in the Western world. The highest incidence rates are found in Japan, North America, parts of Europe, New Zealand, and Australia, and rates are low in Africa and South-East Asia. Rates are substantially higher in men than in women.

About Vectibix

Vectibix is the first fully human anti-EGFR antibody approved by the U.S. Food and Drug Administration (FDA) for the treatment of mCRC. Vectibix was approved in the United States in September 2006 as a monotherapy for the treatment of patients with EGFR expressing mCRC 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 are available that demonstrate an improvement in disease-related symptoms or increased survival with Vectibix. Vectibix has not shown a treatment benefit for patients whose tumors had KRAS mutations in codon codon: see nucleic acid.  12 or 13.

In December 2007, the EMEA (Europe, Middle East, Africa) Refers to that region of the world. For example, one might see products packaged differently for the UK, EMEA and Asia Pacific markets.  granted a conditional marketing authorization for Vectibix as monotherapy for the treatment of patients with EGFR-expressing mCRC with wild-type KRAS genes after failure of standard chemotherapy regimens. Vectibix has been launched in over 20 countries, Switzerland, Australia and Canada. Applications in the rest of the world, including Japan, are pending.

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 greater than or equal to grade 2 within 1 month, permanently discontinue Vectibix. The clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus pruritus /pru·ri·tus/ (proo-ri´tus) itching.prurit´ic

pruritus a´ni  intense chronic itching in the anal region.

pruritus hiema´lis  xerotic eczema.
, erythema erythema (ĕr'əthē`mə), more or less diffuse redness of the skin due to concentration of an abnormally large amount of blood within the small vessels of the skin (hyperemia), as in burns. , rash, skin exfoliation exfoliation /ex·fo·li·a·tion/ (eks-fo?le-a´shun)
1. a falling off in scales or layers.

2. the removal of scales or flakes from the surface of the skin.

3.
, paronychia paronychia /par·onych·ia/ (par?-ah-nik´e-ah) inflammation involving the folds of tissue around the fingernail.

par·o·nych·i·a
n.
Inflammation of the tissue surrounding a nail.
, 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 anaphylactic /ana·phy·lac·tic/ (an?ah-fi-lak´tik) pertaining to anaphylaxis.
anaphylactic (an´
 reactions, bronchospasm bronchospasm /bron·cho·spasm/ (brong´ko-spazm) bronchial spasm; spasmodic contraction of the smooth muscle of the bronchi, as in asthma.

bron·cho·spasm
n.
, and hypotension hypotension
 or low blood pressure

Condition in which blood pressure is abnormally low. It may result from reduced blood volume (e.g., from heavy bleeding or plasma loss after severe burns) or increased blood-vessel capacity (e.g., in syncope).
. 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.

About Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.

Forward-Looking Statements

This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen's most recent annual report on Form 10-K and most recent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of Sept. 24, 2009 and expressly disclaims any duty to update information contained in this news release.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation An action brought in court to enforce a particular right. The act or process of bringing a lawsuit in and of itself; a judicial contest; any dispute.

When a person begins a civil lawsuit, the person enters into a process called litigation.
 and products liability claims. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.

In addition, sales of our products are affected by the reimbursement policies imposed by third-party payors, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and health care cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate im·pli·cate  
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.

2.
 an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.

The scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration (FDA) for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. Only the FDA can determine whether the products are safe and effective for these uses. Healthcare professionals should refer to and rely upon the FDA-approved labeling for the products, and not the information discussed in this news release.

    CONTACT: Amgen, Thousand Oaks
    Christine Regan: +1-805-447-5476 (media U.S.)
    Wendy Woods: +41-(0)-41-3692-542 (media Europe)
    Arvind Sood: +1-805-447-1060 (investors)



(Logo: http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO)

media U.S., Christine Regan, +1-805-447-5476, or media Europe, Wendy Woods, +41-(0)-41-3692-542, or investors, Arvind Sood, +1-805-447-1060, all of Amgen, Thousand Oaks; Photo: http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO
COPYRIGHT 2009 PR Newswire Association LLC
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2009 Gale, Cengage Learning. All rights reserved.

 Reader Opinion

Title:

Comment:



 

Article Details
Printer friendly Cite/link Email Feedback
Publication:PR Newswire Europe
Date:Sep 24, 2009
Words:2243
Previous Article:Node4 : Knowledge Is Power.
Next Article:New Weekly Asia Polyethylene (PE) Pipe Grade Resin Price Report From ICIS Pricing.
Topics:

Terms of use | Copyright © 2014 Farlex, Inc. | Feedback | For webmasters