Amgen announced interim pooled, blinded safety data from two phase 3 trials examining Vectibix (panitumumab) in combination with chemotherapy in first- and second-lines of metastatic colorectal cancer (mCRC) treatment.
The respective independent Data Monitoring Committee's reviews of the pooled, or combined, safety data from both arms of these randomized, multi-centre trials endorsed the continuation of these studies per protocol. These interim data were presented at the 2008 Gastrointestinal Cancers Symposium (ASCO GI) in Orlando, Florida.
Vectibix was approved as a monotherapy in the United States in September 2006 for the treatment of patients with epidermal growth factor receptor- (EGFr) expressing mCRC after disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.
"We continue to make progress in elucidating the potential utility of Vectibix in the treatment of colorectal cancer," said David Chang, M.D., vice president for oncology clinical development at Amgen. "These phase 3 studies will provide important information about the efficacy of Vectibix when used in combination with conventional chemotherapy regimens."
The "PRIME" (Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy) or "203" trial is a global Phase 3 study investigating Vectibix in combination with FOLFOX chemotherapy as a first-line treatment for patients with mCRC. Patients enrolled in the study 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 is progression-free survival and other endpoints include overall survival, objective response rate, time to progression, duration of response and safety.
A pooled interim safety review of 601 patients (302 Vectibix plus FOLFOX; 299 FOLFOX only) of which 99 percent received at least one cycle of therapy showed the following grade 3/4 adverse events: neutropenia (25 percent), diarrhea (10 percent), fatigue (four percent), nausea and pulmonary embolism (three percent, respectively), febrile neutropenia, hypomagnesemia, dehydration and deep vein thrombosis (two percent, respectively). Fifty-four percent of the pooled patient population had a skin reaction with 11 percent of patients having a grade three and less than one percent experiencing a grade four. PRIME study's target accrual goal of approximately 1,150 patients was reached in January 2008.
The "181" trial is a global Phase 3 study investigating Vectibix in combination with FOLFIRI chemotherapy as a second-line treatment for patients with mCRC. Patients enrolled in the study were randomized to receive either 6.0 mg/kg of Vectibix and FOLFIRI Q2W or FOLFIRI Q2W alone. The co-primary endpoints are progression-free survival and overall survival, other endpoints include objective response rate, time to progression, duration of response and safety.
A pooled interim safety review for 701 patients (352 Vectibix plus FOLFIRI; 349 FOLFIRI only) of which 99 percent received at least one cycle of therapy showed the following grade 3/4 adverse events: neutropenia (15 percent), diarrhea (9 percent), fatigue (four percent), febrile neutropenia, nausea, dehydration, pulmonary embolism (two percent, respectively), hypomagnesemia and deep vein thrombosis (one percent, respectively) and infection (less than one percent). Sixty-one percent of the pooled patient population had a skin reaction with 12 percent experiencing a grade three and less than one percent experiencing a grade four. Target accrual for this study is approximately 1,100 patients and enrollment is anticipated to be complete by Q1 2008.
In both arms of each trial KRAS mutational status in patients' tumors will be studied as a biomarker for Vectibix activity. Recent data indicate that KRAS gene status may predict efficacy and could potentially serve as a patient selection biomarker for Vectibix monotherapy.
Vectibix is approved 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. In December 2007, the European Medicines Agency (EMEA) granted a conditional marketing authorization for Vectibix as monotherapy for the treatment of patients with EGFr-expressing mCRC with non-mutated (wild-type) KRAS genes after failure of standard chemotherapy regimens. Regulatory applications in the rest of the world are still pending.
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