Patients with newly diagnosed metastatic colorectal cancer were randomized to treatment with standard chemotherapy (FOLFIRI – irinotecan, 5-FU, leucovorin) with or without cetuximab. Patients receiving cetuximab had an advantage in progression-free survival but not overall survival. The added benefit of cetuximab appeared to be confined to patients whose tumors had wild-type KRAS. Those patients whose tumors had mutant KRAS appeared to have no benefit from the addition of cetuximab. 348 of the 1198 (29%) patients had tumors with wild-type KRAS, and therefore had potential benefit from the addition of cetuximab to chemotherapy. It is clear from this study and others that KRAS is now a standard part of the pathology evaluation of colorectal tumors, with predictive import in regard to EGFR related therapy such as cetuximab. In this study 71% of patients had mutated KRAS and should not receive cetuximab, which has additional toxicity and adds considerably to the cost of therapy. A major question is whether, even for patients with KRAS wild-type tumors, there was sufficient benefit to justify a more toxic and costly treatment. The addition of cetuximab improved progression-free survival from 8.7 to 9.9 months with a hazard ratio of 0.68, which was statistically significant. Overall survival, was lengthened from 21.0 months to 24.9 months by the addition of cetuximab, with a hazard ratio of 0.84, but this extension of survival was not statistically significant. Patients receiving cetuximab had significantly more rash, diarrhea, and infusion reactions. The question of whether these data justify the use of cetuximab in this circumstance is an important one both for patients who will suffer the additional toxicity, and our health care system which will bear the additional cost. This is one of a number of new, expensive, “targeted” agents which have shown improvement in progression-free survival but not overall survival. Lapatinib and bevacizumab were approved for use in patients with metastatic breast cancer, by the FDA with similar data. Other countries such as the United Kingdom and Canada have been much more restrictive in their approval of costly agents in these circumstances. With the costs of healthcare in the US rising rapidly, we may need to be more restrictive in the future. Lawrence N Schulman, MD