Amgen has announced updated interim pooled, blinded, safety results from two phase III trials evaluating Vectibix (panitumumab) in combination with standard chemotherapy in earlier lines of metastatic colorectal cancer (mCRC).
Updated data from these trials, as well as the first prospective trial evaluating the impact of the clinical biomarker KRAS on Vectibix efficacy in combination with chemotherapy, were presented at the 2008 American Society of Clinical Oncology's (ASCO) Annual Meeting in Chicago.
"The data being generated from a number of our ongoing trials in various settings of colorectal cancer continue to inform us about the safety of Vectibix in combination with standard chemotherapy," said Roger M Perlmutter, MD, Ph.D., executive vice president of research and development at Amgen. "Our data regarding the importance of KRAS mutation status emphasize the significance of this biomarker in developing individualized therapy for colorectal cancer".
The 'PRIME' or 20050203 study is a global, phase III trial investigating Vectibix in combination with Folfox chemotherapy as first-line treatment for mCRC among wild-type KRAS and all randomized patients. Final enrolment was completed in February 2008 with a total of 1,183 patients.
Pooled safety data from a planned interim analysis, conducted by an independent Data Monitoring Committee (DMC), of 903 patients (455 Vectibix plus Folfox; 448 Folfox only), of which 99 per cent received at least one cycle of therapy, showed the following pooled grade 3/4 adverse events: neutropenia (28 percent), diarrhoea (11 percent), fatigue (4 percent), nausea (3 percent), dehydration (3 percent) and hypomagnesaemia, pulmonary embolism, febrile neutropenia and deep vein thrombosis (2 percent, respectively). Fifty-six per cent of the pooled patient population had skin and subcutaneous tissue system organ class (SOC) events of any grade; 10 percent grade 3 and less than one percent grade. Based upon this interim safety analysis, the DMC recommended that the PRIME study continue per protocol.
Patients enrolled in this study were randomized to receive either 6.0 mg/kg of Vectibix and Folfox once every two weeks (Q2W) or Folfox alone Q2W. The primary endpoint is progression-free survival (PFS). Other endpoints include overall survival, objective response rate, time to progression, duration of response and safety.
All study endpoints will be investigated by patients' KRAS mutational status in both treatment arms as a biomarker for Vectibix activity in combination with Folfox chemotherapy as first-line treatment for mCRC.
"These data are the first to measure the potential impact of KRAS status in combination treatment with Vectibix and chemotherapy, and add to the growing body of evidence that help validate KRAS as a potential patient selection biomarker for anti-EGFr therapy," said Allen Cohn, MD, Rocky Mountain Cancer Center, US Oncology, Denver, Colorado. "KRAS mutational status ranks among one of the most important scientific advances in colorectal cancer and has the potential to redefine how these patients are currently treated".
Vectibix is the EGFr-inhibitor of choice in the treatment of advanced colorectal cancer patients who have failed standard chemotherapy due to its demonstrated efficacy, safety and convenient Q2W dosing schedule.