Vectibix(R) Now Available For The Treatment Of Advanced Colorectal Cancer In Belgium

Main Category: Colorectal Cancer
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 03 Oct 2008 - 6:00 PDT

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Amgen Belgium announces the availability of Vectibix® (panitumumab), the first fully human anti-EGFR monoclonal antibody indicated as monotherapy for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) with non-mutated (wild-type) KRASgene after failure of fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy protocols.

"I am pleased that we can now offer our patients a new targeted, effective treatment option in an advanced disease such as stage IV colorectal cancer, " said Prof Marc Peeters, coordinator of the oncology unit at the university hospital of Gent. "The availability of Vectibix in Belgium with reimbursement represents an exciting move to an individualized medicine especially for a patient population with, so far, limited therapeutic options.

The KRASbiomarker helps improve patient selection and response. By targeting Vectibix treatment on patients with non-mutated KRAS, clinicians can maximize response rates, disease control and progression-free survival avoiding unnecessary side effects and costs in patients for whom treatment is not appropriate.

"Amgen is committed to identifying, validating and implementing novel, clinically relevant biomarkers to help physicians select the right treatment for patients," said Marco Liguori, General Director of Amgen Belgium. "By introducing Vectibix®, Amgen is paving the way for the development of increasingly targeted and personalized new-generation molecules"

The correlation between KRASgene mutation in tumor cells and the sensitivity to treatment with an anti-EGFR agent was demonstrated for the first time in a randomized study by Amgen in a large number of patients (427). KRASgene mutations have been identified as being responsible for failure to anti-EGFR antibody therapy. It is therefore essential to identify whether or not a patient's tumor presents this mutation, so that the therapeutic strategy can be adapted accordingly.

Vectibix monotherapy doubled median progression-free survival in refractory metastatic colorectal carcinoma patients with non-mutated KRAScompared to patients receiving Best Supportive Care (BSC) alone (16 weeks vs 8 weeks). At two months the cancer in patients treated with panitumumab and BSC was three times less likely to have progressed compared to BSC alone i.e. cancer had not progressed in 60 percent of patients treated with Vectibix plus BSC vs 21 percent with BSC alone. At six months the cancer in patients treated with panitumumab and BSC was approximately four times less likely to have progressed compared to BSC alone i.e. cancer had not progressed in 22 percent of patients treated with Vectibix plus BSC vs 6 percent with BSC alone.1

Vectibix was generated with the Xenomouse technology which produces 100% human monoclonal antibodies that contain no murine protein. The total absence of murine protein lessens the risk of immune responses when the product is infused (less than 1% severe infusion reaction).

About KRAS

KRASplays an important role in cell growth regulation and oncogenesis. Anti-EGFr therapies work by blocking the activation of EGFr, thereby inhibiting downstream events that lead to growth signaling. However, in patients with tumors harboring a mutated KRAS, the KRASprotein is always turned "on" regardless of whether EGFr has been activated or therapeutically inhibited. Thus, in patients with mutated KRAS, signaling continues despite anti-EGFr therapy. Mutant KRASis detected in approximately 40 percent of CRC tumors.

About the Biomarker Analysis

These biomarker data were generated from a pre-specified analysis of the phase 3, randomized, controlled clinical trial "408" that investigated the treatment effect of KRASstatus (non-mutated versus mutated) in Vectibix patients with mCRC. The analysis demonstrated that the effect of Vectibix on progression-free survival (PFS) was confined exclusively to the approximately 60 percent of patients whose tumors harbor normal, non-mutated (wild-type) KRAS. Vectibix had no clinical benefit in patients who had tumors with mutations in KRASregardless of the endpoint studied. Previously reported pivotal results from "408" demonstrated that Vectibix monotherapy significantly improved PFS and response rates in heavily pre-treated patients with mCRC after failure of standard chemotherapy versus best supportive care.

About Vectibix

Vectibix the first fully human IgG2 monoclonal antibody (MAb), targets the EGFr, a protein that plays an important role in cancer cell growth regulation and carcinogenesis. With its demonstrated efficacy, low rate of infusion reactions and immunogenicity, and convenient Q2W dosing schedule Vectibix provides an important option in the management of metastatic CRC patients.

In the EU, Vectibix is indicated as monotherapy for the treatment of patients with metastatic colorectal carcinoma expressing EGFr with tumors with non-mutated KRASand after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens

Approved by the Food and Drug Administration (FDA) in September 2006, Vectibix is indicated in the United States (U.S.) as a single agent for the treatment of EGFR-expressing, metastatic colorectal carcinoma (mCRC) with 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. Inherent to the cross-over design of the 408 study, no data are available that demonstrate an increased survival with Vectibix.

Ongoing Phase 3 trials are exploring the potential of administering Vectibix in combination with chemotherapy for first- and second-line mCRC, as well as in the head and neck cancer setting.

Important Product Safety Information EU

Related dermatological reactions, a pharmacologic class effect observed with epidermal growth factor receptor (EGFr) inhibitors, are experienced with nearly all patients (approximately 90 percent) treated with Vectibix. The majority of dermatological reactions are mild to moderate in nature In clinical studies, subsequent to the development of severe dermatological reactions, infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported. Patients who have severe dermatologic reactions or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae, and appropriate treatment promptly initiated.

Severe infusion reactions occurred with Vectibix in approximately one percent of patients. Severe infusion reactions were identified as anaphylactic reactions, bronchospasm, fever, chills and hypotension. Although fatal infusion reactions have not been reported with Vectibix, they have occurred with other monoclonal antibody products. Severe infusion reactions require stopping the infusion and possibly permanently discontinuing Vectibix, depending on the severity and / or persistence of the reaction.

About Colorectal Cancer

Colorectal cancer is a disease in which malignant cells form in the colon or rectum. This type of cancer begins in the digestive system, also called the GI (gastrointestinal) system. The cancer can start in any part of the colon or rectum. The wall of colon and rectum has several layers of tissues. Colorectal cancer starts in the inner layer and can grow through some or all of the other layers. The stage of the cancer largely depends on which of these layers is affected.[1]

In most cases, colorectal cancer develops slowly over several years. Most of these cancers begin as a polyp - a mass of tissue that projects into the lumen of the colorectum. Removing the polyp early may prevent it from becoming cancer.

-- Metastatic colorectal cancer is cancer that has started in the colon or rectum, and spread beyond nearby lymph nodes to other parts of the body. Metastatic colorectal cancer is also called "advanced disease," and is known as Stage IV colorectal cancer.

 --  Colorectal cancer is the third most common cancer worldwide in men and the second most common in women.[2] In Belgium over 8000 new cases of colorectal cancer were diagnosed every year.

About Amgen

Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realise the new science's promise by bringing safe, effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics has 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 http://www.amgen.com.

Forward Looking Statements

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References

[1] American Cancer Society website.
[2] Boyle, P. Cancer incidence and mortality in Europe, 2004. International Agency for Research on Cancer. 2004, p.483.

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