NEW YORK -- ImClone Systems Incorporated and Bristol-Myers Squibb Company announced results from a multicenter, open-label, randomized Phase III trial, published in the Nov. 14 New England Journal of Medicine, in which ERBITUX® (cetuximab) as a single agent demonstrated a significant improvement in overall survival in patients with metastatic colorectal cancer (mCRC) refractory to approved chemotherapy agents. The study compared ERBITUX plus best supportive care (BSC) to BSC alone in patients with mCRC whose disease had progressed through treatment with all approved chemotherapy, including irinotecan, oxaliplatin, and fluoropyrimidines.
The independent study (NCIC CTG CO.17), conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG), involved 572 patients and demonstrated that treating patients with ERBITUX as a monotherapy plus BSC significantly increased overall survival compared to BSC alone. BSC included palliative therapies designed to alleviate pain and treat other effects caused by mCRC.
"This is the first time an antibody used as a single agent in colorectal cancer has demonstrated an overall survival benefit. These outcomes add to the growing body of evidence supporting the significant clinical benefits of ERBITUX," said Eric K. Rowinsky, MD, chief medical officer and senior vice president of ImClone Systems.
"These data demonstrate that ERBITUX may provide certain colorectal cancer patients with additional time -- even when other available treatment options have failed," said Maurizio Voi, MD, executive director, Oncology Global Medical Affairs, Bristol-Myers Squibb. "The results are part of our comprehensive clinical development program designed to fully understand the potential uses of ERBITUX."
The study enrolled patients with epidermal growth factor receptor (EGFR)- expressing metastatic colorectal cancer who had been previously treated. ERBITUX was administered at the recommended dose and schedule: 400 mg/m2 initial dose, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicity.
In this study, the median survival was 6.1 months for patients treated with ERBITUX plus BSC versus 4.6 months for patients on BSC alone (Hazard Ratio: 0.77, P=0.005). Treatment with ERBITUX monotherapy resulted in a significant improvement in progression-free survival versus BSC alone (Hazard Ratio: 0.68, P<0.001). Twenty-three patients (8.0 percent) treated with ERBITUX and no patients on BSC alone had partial responses (P<0.001).
Grade 3/4 adverse events (occurring in greater than or equal to 10 percent of patients in either group) reported more frequently in the ERBITUX plus BSC treatment arm compared with the BSC only arm included fatigue (33 percent vs 26 percent), other pain (16 percent vs 7 percent), dyspnea (16 percent vs 12 percent), infection without neutropenia (13 percent vs 6 percent), rash/desquamantion (12 percent vs <1 percent), and other gastrointestinal (10 percent vs 8 percent).
Grade 3/4 infusion reactions (hypersensitivity) occurred in 5 percent of patients in the ERBITUX plus BSC arm. The most common (occurring in greater than or equal to 25 percent of patients in either group) adverse events of any grade were rash/desquamation, fatigue, abdominal pain, other pain, dry skin, dyspnea, constipation, pruritus, diarrhea, vomiting, infection without neutropenia, headache, fever, insomnia, cough, other dermatology, and stomatitis.
This study supported the recent label change for ERBITUX -- approved by the U.S. Food and Drug Administration on October 2, 2007 -- to include overall survival data as a monotherapy agent in patients with EGFR-expressing mCRC after failure of irinotecan- and oxaliplatin-based chemotherapy regimens.
Source: Bristol-Myers Squibb; ImClone Systems Incorporated