Interaction with oxaliplatin with cetuximab

There has been some concern mounting over the past few years that there may be important interactions with EGFR based antibodies and cytotoxic chemotherapy, especially oxaliplatin (Eloxatin, Sanofi-Aventis). There were several abstracts presented at ASCO this year that help illuminate the situation. I also refer you to a quick poster discussion by discussant Jeffrey Meyerhardt available via Virtual Meeting access. The two larger studies are discussed here.

Dr. Volker Heineman et al presented their study in first line therapy of metastatic colorectal cancer with XELIRI (or do you say CapeIri?) or XELOX (CapeOx?) with cetuximab. This was a randomized, phase-3, multicenter clinical trial. The upshot was that response rate was about the same in both arms, but the time to progression was lower than expected with each treatment (8.4 months and 9.2 months, respectively). There was also more toxicity in the oxaliplatin arm, a recurring theme in EGFR combination trials.

Dr. Tudor Ciuleanu, et al, presented their data on a randomized phase-2 study of FOLFIRI/cetuximab or FOLFOX6/cetuximab for first line metastatic colorectal cancer. Again, response rate was similar in each arm. Nine month progression free survival was also similar. More toxicity was seen in the oxaliplatin arm as well.

These studies, as well as some prior work, have raised some questions in my mind about the cooperative group study, CALGB 80405, where patients are treated with FOLFIRI or FOLFOX (physician choice) and then randomized to bevacizumab (Avastin, Genentech), cetuximab (Erbitux, ImClone) or both. I think the weight of the data suggest that it is appropriate to continue to accrue to 80,405, but I look forward to an interim analysis to give some early signals about the cetuximab-oxaliplatin arm. Also, I think it goes without saying that it is best not to use cetuximab in front-line therapy or with oxaliplatin off study.