Final Vectibix Positive Pivotal Phase 3 Trial Results In Metastatic Colorectal Cancer Patients Published
"Medical advances in the treatment of first- and second-line colorectal cancer have improved survival rates; however, most patients develop resistance to these therapies, creating the need for an active agent to treat patients with advanced disease," said Professor Eric Van Cutsem, M.D., Ph.D., Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium, lead author of the manuscript. "Final results from the first large randomized trial of its kind show that Vectibix provides a benefit in this heavily pre-treated patient population."
The September 2006 Food and Drug Administration (FDA) approval of Vectibix was based on the results from this multi-national, open-label, randomized study of 463 patients. Patients were randomized to receive 6 mg/kg Vectibix plus BSC (n=231) every two weeks or BSC alone (n=232) until disease progression or unacceptable toxicity. An independent, central radiology review board assessed disease progression and tumor shrinkage. BSC patients determined to have disease progression were eligible to cross-over to a separate study and receive Vectibix.
The primary endpoint of this study was an improvement in progression-free survival. Co-secondary study endpoints were best objective response by blinded central review and overall survival time. The effectiveness of Vectibix for the treatment of EGFr-expressing, metastatic colorectal cancer is based on progression-free survival. Currently no data are available that demonstrate increased survival with Vectibix.
As seen in previous analyses of these data, the Vectibix group showed a statistically significant improvement in progression-free survival versus those who received BSC alone yielding a 46 percent decrease in the relative progression rate. The mean progression-free survival was 96 versus 60 days.
A blinded central review showed that 10 percent of patients in the Vectibix group had an objective response, while no patients in the BSC group demonstrated an objective response. Median time to response was 7.9 weeks and median duration of response was 17 weeks.
In the BSC group 174 (75 percent) patients received Vectibix under the crossover protocol. In those patients that crossed over, the objective response rate was 10 percent. The median time to crossover was 7.0 (6.6, 7.3) weeks. The median follow-up after crossover was 27 (4-69) weeks.
In the primary analysis of overall survival, there was no significant difference between the groups. The median follow-up time was 72 weeks for all patients.
A broadly-based clinical development program designed to examine the utility of Vectibix in the first- and second-line treatment of metastatic colorectal cancer, as well as head and neck cancer is ongoing.
Important Product Safety Information
As described below, the Vectibix Prescribing Information includes warning language:
Dermatologic toxicities, related to Vectibix blockade of EGF binding and subsequent inhibition of EGFr-mediated signaling pathways, were reported in 89 percent of patients and were severe (NCI-CTC grade 3 and higher) in 12 percent of patients receiving Vectibix monotherapy. The clinical manifestations included, but were not limited to, dermatitis acneiform, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Severe dermatologic toxicities were complicated by infection, including sepsis, septic death, and abscesses requiring incisions and drainage. Vectibix may need to be withheld or discontinued for severe dermatologic toxicities.
Severe infusion reactions occurred with Vectibix in approximately 1 percent of patients. Severe infusion reactions were identified by reports of anaphylactic reaction, bronchospasm, fever, chills, and hypotension. Although fatal infusion reactions have not been reported with Vectibix, fatalities 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.
Other important safety information includes:
The most common adverse reactions observed with Vectibix were skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea and diarrhea. Hypomagnesemia occurred 6 weeks or longer after the initiation of Vectibix. In some patients, hypomagnesemia was associated with hypocalcemia.
Vectibix is indicated for the treatment of EGFr-expressing, metastatic colorectal cancer with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
The effectiveness of Vectibix for the treatment of EGFr-expressing, metastatic colorectal cancer is based on progression-free survival. Currently no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Vectibix.
AmgenTM Oncology Assistance
Amgen has expanded its patient assistance programs into a comprehensive, multifaceted program with a single gateway - AmgenTM Oncology Assistance. Through this program, patients who are uninsured, underinsured, or unable to afford their insurance co-payments can receive financial support for Amgen's cancer medicines, including Vectibix. The Amgen Oncology Assistance program will be available for U.S. cancer patients and will launch in October. For more information, please visit www.amgen.com.
About Colorectal Cancer
Colorectal cancer is the third most common cancer diagnosed in men and in women in the United States. The American Cancer Society estimated that about 112,340 new cases of colon cancer and 41,420 new cases of rectal cancer will be diagnosed in 2007. Colorectal cancer is the second leading cause of cancer death among men and women in the United States and Canada (after lung cancer). It has been estimated that 52,180 people will die from colorectal cancer in 2007. That means that one person in the United States dies of colorectal cancer every 9.3 minutes.
Although EGF receptors normally help regulate the growth of many different cells in the body, these receptors also can stimulate cancer cells to grow. In fact, some cancer cells actually require signals mediated by EGF receptors for their survival. Residing on the surfaces of these tumor cells, EGF receptors are activated when naturally occurring proteins in the body, such as epidermal growth factor (EGF) or transforming growth factor alpha (TGF-alpha), bind to them. This binding changes the shape of the EGF receptors, which, in turn, triggers internal cellular signals that stimulate tumor cell growth. Vectibix binds to EGF receptors, preventing the natural ligands such as EGF and TGF-alpha from binding to the receptors and interfering with the signals that might otherwise stimulate growth and survival of the cancer cell.
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Posted: May 2007