Researchers involved in the Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) trial have reported that the addition of Vectibix (panitumumab) to chemotherapy plus Avastin (bevacizumab) does not improve outcomes of patients with metastatic colorectal cancer. The details of this study were presented at the 9th World Congress on Gastrointestinal Cancer in Barcelona, June 28- July 1, 2007.

Vectibix is the first entirely humanized monoclonal antibody targeting the epidermal growth factor receptor (EGFR) approved by the US Food and Drug Administration (FDA). Vectibix is approved for EGFR-expressing, metastatic colorectal cancer that has progressed while on treatment, or following therapy, with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Results from clinical trials have demonstrated an improvement in progression-free survival with the use of Vectibix compared to best supportive care in metastatic colorectal cancer.

Patients in this study had metastatic colorectal cancer and had not received prior chemotherapy or biologic therapy. Patients received one of two chemotherapy regimens based on physician choice: FOLFOX (5-FU, oxaliplatin, leucovorin) or FOLFIRI (5-FU, irinotecan and leucovorin). All patients received Avastin. Patients were randomly allocated to receive Vectibix or no further therapy. This study enrolled 800 patients and an ongoing review revealed an increase in diarrhea, dehydration, and infection in the group receiving Vectibix. In March 2007, a planned interim review of the data after 231 events showed worse outcomes in the Vectibix treated patients and the study was discontinued.

The following table summarizes the results of the interim analysis of this study which only includes data on patients receiving FOLFOX and not those receiving FOLFIRI.

These authors reported that outcomes were worse for patients over the age of 80 years, those with a higher ECOG score and those with significant co-morbidities. They also reported more dose reductions and delay of Avastin administration in the patients receiving Vectibix. These authors concluded that the addition of Vectibix to Avastin and oxaliplatin-based chemotherapy results in increased toxicity. They also concluded that there were no signs of synergistic anti-tumor activity. They speculated that Vectibix increased toxicity in vulnerable populations while only a minority might benefit from adding EGFR inhibition. Further data including molecular analyses and data from the irinotecan cohort are forthcoming.

Comments: This study shows the difficulty of combining biological agents even when there is a good rationale.

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