EORTC BOS 2 trial evaluating targeted agents for patients with resectable liver metastases from colorectal cancer

Colorectal cancer (CRC) is the second most frequent cause of cancer-related mortality in both Europe and the United States. Treatment for patients with resectable hepatic metastases from colorectal cancer consists of surgery combined with chemotherapy, but recurrence is observed in two thirds of these patients. In order to improve the outcome for these patients, EORTC trial 40091 – BOS 2 will test the efficacy of adding bevacizumab or panitumumab to the standard treatment, peri-operative FOLFOX 4 chemotherapy.

Bevacizumab is a monoclonal antibody which targets the vascular endothelial growth factor (VEGF), and blocking VEGF could deprive the cancer of required nutrients. Panitumumab targets the epidermal growth factor receptor (EGFR). EGFR gene expression is upregulated in approximately 60 to 80% of CRC cases, and this has been linked to poor survival.

Dr. Bernard Nordlinger, CHU Ambroise Pare AP-HP, Boulogne-Billancourt and Coordinator of this study, says “The objective of this trial is to determine a new standard of care for these patients.” The randomized phase 2 EORTC trial will investigate if treatment with perioperative modified FOLFOX6 plus either bevacizumab or panitumumab improves progression-free survival and pathological response in patients with up to eight resectable liver metastases resulting from wild type KRAS CRC as compared to treatment with perioperative modified FOLFOX 6 alone.

Dr. Stephane Benoist, Assistance Publique, Hôpitaux de Paris, Hopital De Bicetre AP-HP, Le Kremlin Bicetre and co-Coordinator of this study, says “Following the EPOC study, perioperative FOLFOX chemotherapy became the new standard of care in many countries for patients with resectable colorectal liver metastases. Nevertheless, most patients developed recurrence despite perioperative FOLFOX chemotherapy. One of the ways to improve long term prognosis is to intensify the perioperative chemotherapy. The BOS 2 study addresses a major clinical question: is there any benefit from intensifying perioperative FOLFOX chemotherapy by adding biological therapy? Translational research projects that are part of this study will determine, for the first time, whether pathological response to preoperative chemotherapy could be a predictor of progression-free survival in resected patients, whether assessment of metabolic response by FDG-PET/CT after one course of chemotherapy could be an early predictor of no response, and whether biological subgroups in wild type KRAS patients would benefit more from one of the regimens. Overall, the BOS 2 study should be an important step towards improving the therapeutic management and long term prognosis of patients with resectable colorectal liver metastases.”

The EORTC BOS 2 trial plans to accrue 360 patients in 50 sites located in ten countries: France, Belgium, Germany, The Netherlands, the United Kingdom, Spain, Austria, Switzerland, Sweden, and Norway. This EORTC trial is partially supported by unrestricted educational grants from Amgen and Roche.

For more information concerning EORTC trial 40091 – BOS 2 please contact: www.eortc.org/contact

John Bean, PhD
EORTC, Medical Science Writer