Pivotal Study Meets Primary Endpoint of Progression-Free Survival in Wild-Type KRAS
Population Phase 3 Results Reinforce Importance of KRAS Testing
THOUSAND OAKS, CA, USA | August 6, 2009 | Amgen (Nasdaq: AMGN) today announced that Vectibix (panitumumab), administered in combination with FOLFOX (an oxaliplatin-based chemotherapy), significantly prolonged progression-free survival (PFS) compared with FOLFOX alone in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer (mCRC).
"We believe that these data document an important advance for patients with metastatic colorectal cancer," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "These are the first prospective Phase 3 data to demonstrate the utility of KRAS mutational analysis as a predictive biomarker."
Overall, the adverse event profile was as anticipated for an anti-EGFR antibody in combination with oxaliplatin-based chemotherapy, including known events such as skin toxicity, hypomagnesemia and diarrhea.
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 the 1,183 patients enrolled in the trial.
Importantly, in patients with tumors harboring activating KRAS mutations, PFS was significantly inferior in the Vectibix arm. These data confirm previous findings when oxaliplatin-based chemotherapy and an anti-EGFR antibody are combined.
"Our study underscores the importance of KRAS status in identifying the appropriate patient population to be treated with Vectibix, consistent with worldwide labeling," said Perlmutter. "Not only is the improvement in progression-free survival limited to patients with wild-type KRAS tumors, but patients with KRAS mutant tumors were negatively affected when Vectibix was added to a standard chemotherapy regimen. We believe Vectibix should not be used in patients with tumors containing activating KRAS mutations."
Detailed efficacy and safety data according to KRAS status will be submitted for presentation at an upcoming medical congress.
Study Design
PRIME (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) enrolled 1,183 patients globally. Patients 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, 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 12 or 13.
In December 2007, the EMEA 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 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 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.
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.
SOURCE Amgen
Post Views: 38
Pivotal Study Meets Primary Endpoint of Progression-Free Survival in Wild-Type KRAS
Population Phase 3 Results Reinforce Importance of KRAS Testing
THOUSAND OAKS, CA, USA | August 6, 2009 | Amgen (Nasdaq: AMGN) today announced that Vectibix (panitumumab), administered in combination with FOLFOX (an oxaliplatin-based chemotherapy), significantly prolonged progression-free survival (PFS) compared with FOLFOX alone in the first-line treatment of patients with KRAS wild-type metastatic colorectal cancer (mCRC).
"We believe that these data document an important advance for patients with metastatic colorectal cancer," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "These are the first prospective Phase 3 data to demonstrate the utility of KRAS mutational analysis as a predictive biomarker."
Overall, the adverse event profile was as anticipated for an anti-EGFR antibody in combination with oxaliplatin-based chemotherapy, including known events such as skin toxicity, hypomagnesemia and diarrhea.
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 the 1,183 patients enrolled in the trial.
Importantly, in patients with tumors harboring activating KRAS mutations, PFS was significantly inferior in the Vectibix arm. These data confirm previous findings when oxaliplatin-based chemotherapy and an anti-EGFR antibody are combined.
"Our study underscores the importance of KRAS status in identifying the appropriate patient population to be treated with Vectibix, consistent with worldwide labeling," said Perlmutter. "Not only is the improvement in progression-free survival limited to patients with wild-type KRAS tumors, but patients with KRAS mutant tumors were negatively affected when Vectibix was added to a standard chemotherapy regimen. We believe Vectibix should not be used in patients with tumors containing activating KRAS mutations."
Detailed efficacy and safety data according to KRAS status will be submitted for presentation at an upcoming medical congress.
Study Design
PRIME (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) enrolled 1,183 patients globally. Patients 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, 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 12 or 13.
In December 2007, the EMEA 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 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 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.
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.
SOURCE Amgen
Post Views: 38
