THOUSAND OAKS, Calif., Aug. 17 /PRNewswire-FirstCall/ -- Amgen (Nasdaq: AMGN) today announced positive top-line results from a Phase 3 trial evaluating Vectibix((R) )(panitumumab) in combination with FOLFIRI (an irinotecan-based chemotherapy) as a second-line treatment in 1,186 patients with metastatic colorectal cancer (mCRC). The co-primary endpoints, tested independently, were progression-free and overall survival.
Vectibix significantly improved progression-free survival in combination with FOLFIRI, compared to FOLFIRI alone, in patients with KRAS wild-type mCRC. Although numerically greater, the improvement in median overall survival did not achieve statistical significance in the Vectibix arm.
The addition of Vectibix had no positive or negative effect on progression-free or overall survival in patients with tumors harboring activating KRAS mutations.
"With these data, Vectibix has now demonstrated improved progression-free survival in Phase 3 trials in patients with KRAS wild-type tumors in both first- and second-line treatment of metastatic colorectal cancer," said Roger M. Perlmutter, M.D., Ph.D. executive vice president of Research and Development at Amgen. "These results add to the growing body of evidence confirming the utility of KRAS as a predictive biomarker."
Overall, the adverse event profile was as anticipated for an anti-EGFR antibody in combination with irinotecan-based chemotherapy, including known events such as skin toxicity, diarrhea and hypomagnesemia.
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 more than 90 percent of patients enrolled in this trial.
Recently, the Company announced Phase 3 results from a first-line "203" trial which showed that Vectibix significantly improved progression-free survival in mCRC patients with KRAS wild-type tumors in combination with FOLFOX (an oxaliplatin-based chemotherapy).
Detailed efficacy and safety data from both studies will be presented at Europe's largest cancer conference, ECCO 15 - ESMO 34, in September 2009.
The "181" trial is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study. Patients enrolled in the study (n=1,186) were randomized to receive either 6.0 mg/kg of Vectibix and FOLFIRI every two weeks (Q2W) or FOLFIRI alone Q2W. The independently tested co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include objective response rate, time to progression, duration of response and safety by KRAS status.
Results from studies performed over the last twenty-five years indicate that KRAS plays an important role in cell growth regulation. In mCRC, the EGFR transmits signals through a set of intracellular proteins. Upon reaching the nucleus, these signals instruct the cancer cell to reproduce and metastasize, leading to cancer progression. Anti-EGFR 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.
Vectibix is the first fully human anti-EGFR 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.
In December 2007, the EMEA granted a conditional marketing authorization for Vectibix as monotherapy for the treatment of patients with EGFR-expressing metastatic colorectal cancer (mCRC) with wild-type KRAS genes after failure of standard chemotherapy regimens. Vectibix has been launched in over 20 countries, including Switzerland, Australia and Canada. Applications in the rest of the world are pending.
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 12 or 13.
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.
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.
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