Keytruda: Exceptional early results in a small colorectal cancer population

Conclusion: Keytruda (pembrolizumab) is highly efficacious in a subset of colorectal cancer patients that are heavily pretreated, have metastatic disease, and have mismatch repair deficiency. Despite a very high price for a course of therapy, the clinical results overwhelmingly favor pembrolizumab’s use over best supportive care in this subpopulation.

Results were recently published of Keytruda (pembrolizumab) in metastatic colorectal cancer patients who had been treated with a median of four prior therapies. In such a sick and heavily pretreated patient population, it would not be expected that any therapy would make a significant difference, and for most colorectal cancer patients that is the case. However, for a low single-digit percentage of them who are mismatch repair-deficient, pembrolizumab is highly effective. Limited Phase II data show a clinically significant overall response rate, along with exceptionally promising trends in progression-free survival and overall survival. Despite a steep $350,000 pre-discount price for a 20-week course of therapy, the percent reduction in unmet medical need is a highly innovative 35%.

We project that Keytruda will extend median overall survival by 1 to 2 years as opposed to the handful of months to be expected with best supportive care. Survival data in the mismatch repair-proficient population were not nearly as impressive, with clinical performance probably not sufficient to offset the price. We expect pembrolizumab will achieve a label in mismatch repair-deficient colorectal cancer, and will become the standard of care. Furthermore, we expect pembrolizumab will eventually be used in earlier lines of therapy, and testing for mismatch repair deficiency will become far more common.