Amgen announced detailed results from the Phase 3 ‘181’ trial evaluating Vectibix((R)) (panitumumab) in combination with FOLFIRI (an irinotecan based chemotherapy), as a second-line treatment for metastatic colorectal cancer (mCRC)
THOUSAND OAKS, CA, USA | September 22, 2009 | Amgen (Nasdaq: AMGN) today announced detailed results from the Phase 3 ‘181’ trial evaluating Vectibix((R)) (panitumumab) in combination with FOLFIRI (an irinotecan based chemotherapy), as a second-line treatment for metastatic colorectal cancer (mCRC). In this trial, Vectibix significantly improved progression-free survival (PFS) in patients with KRAS wild-type mCRC. These results were presented at the 2009 ECCO 15 – ESMO 34 European Multidisciplinary Congress in Berlin, Germany (Abstract Number 14LBA).
The addition of Vectibix to FOLFIRI significantly improved median PFS (co-primary endpoint) by two months (5.9 versus 3.9 months for patients treated with FOLFIRI alone, hazard ratio 0.73, p=0.004) in patients with KRAS wild-type mCRC. Although numerically greater (14.5 months versus 12.5 months; hazard ratio 0.85), the improvement in median overall survival (co-primary endpoint) in the Vectibix arm did not achieve statistical significance (p=0.115) in the same patient population.
Further, the addition of Vectibix to FOLFIRI resulted in greater than a three-fold improvement (35 percent versus 10 percent) in response rate in the KRAS wild-type patient population as measured by a blinded central review.
"This study showed that Vectibix can be safely administered in combination with FOLFIRI chemotherapy. Vectibix delayed disease progression by more than half compared to FOLFIRI alone in patients with previously treated KRAS wild-type colorectal cancer," said Marc Peeters, M.D., Ph.D., coordinator of Digestive Oncology Unit, University Hospital Ghent and the study’s principal investigator. "Further, the response rate seen in this trial is among the highest ever reported in the second-line metastatic CRC setting."
In general, adverse events 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 3/4 infusion reactions were reported in less than one percent of patients.
There were no differences in progression-free survival, overall survival and response rates among patients with mutated KRAS who received Vectibix.
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 91 percent of the 1,186 patients enrolled in this trial, the highest number ever reported for a second-line trial.
"These high quality prospectively defined analyses prove the clinical utility of KRAS as a predictive biomarker in metastatic colorectal cancer patients," added Peeters.
Study Design
The "181" trial is a global, multicenter, randomized Phase 3 study. Patients enrolled in the study 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 were progression-free survival and overall survival. Secondary endpoints included objective response rate, time to progression, duration of response and safety by KRAS status.
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, 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 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
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Amgen announced detailed results from the Phase 3 ‘181’ trial evaluating Vectibix((R)) (panitumumab) in combination with FOLFIRI (an irinotecan based chemotherapy), as a second-line treatment for metastatic colorectal cancer (mCRC)
THOUSAND OAKS, CA, USA | September 22, 2009 | Amgen (Nasdaq: AMGN) today announced detailed results from the Phase 3 ‘181’ trial evaluating Vectibix((R)) (panitumumab) in combination with FOLFIRI (an irinotecan based chemotherapy), as a second-line treatment for metastatic colorectal cancer (mCRC). In this trial, Vectibix significantly improved progression-free survival (PFS) in patients with KRAS wild-type mCRC. These results were presented at the 2009 ECCO 15 – ESMO 34 European Multidisciplinary Congress in Berlin, Germany (Abstract Number 14LBA).
The addition of Vectibix to FOLFIRI significantly improved median PFS (co-primary endpoint) by two months (5.9 versus 3.9 months for patients treated with FOLFIRI alone, hazard ratio 0.73, p=0.004) in patients with KRAS wild-type mCRC. Although numerically greater (14.5 months versus 12.5 months; hazard ratio 0.85), the improvement in median overall survival (co-primary endpoint) in the Vectibix arm did not achieve statistical significance (p=0.115) in the same patient population.
Further, the addition of Vectibix to FOLFIRI resulted in greater than a three-fold improvement (35 percent versus 10 percent) in response rate in the KRAS wild-type patient population as measured by a blinded central review.
"This study showed that Vectibix can be safely administered in combination with FOLFIRI chemotherapy. Vectibix delayed disease progression by more than half compared to FOLFIRI alone in patients with previously treated KRAS wild-type colorectal cancer," said Marc Peeters, M.D., Ph.D., coordinator of Digestive Oncology Unit, University Hospital Ghent and the study’s principal investigator. "Further, the response rate seen in this trial is among the highest ever reported in the second-line metastatic CRC setting."
In general, adverse events 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 3/4 infusion reactions were reported in less than one percent of patients.
There were no differences in progression-free survival, overall survival and response rates among patients with mutated KRAS who received Vectibix.
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 91 percent of the 1,186 patients enrolled in this trial, the highest number ever reported for a second-line trial.
"These high quality prospectively defined analyses prove the clinical utility of KRAS as a predictive biomarker in metastatic colorectal cancer patients," added Peeters.
Study Design
The "181" trial is a global, multicenter, randomized Phase 3 study. Patients enrolled in the study 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 were progression-free survival and overall survival. Secondary endpoints included objective response rate, time to progression, duration of response and safety by KRAS status.
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, 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 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: 50
