Merck's Keytruda has been approved by the FDA for patients with a microsatellite instability-high (also known as MSI-H) or a mismatch repair deficient (dMMR) biomarker following progression on a fluoropyrimidine, oxaliplatin, and irinotecan. This marks an unprecedented step for the FDA, as it is the first time they have approved a cancer drug based on genetics rather than tumor location.

“The FDA approval of Merck’s Keytruda is a game changer for both our colorectal cancer community as well as the cancer community at-large," said Michael Sapienza, Colon Cancer Alliance CEO. "While the results from Keytruda’s recent clinical trial are incredibly promising, the biggest victory here is that this approval sets a precedent for expedited approval for other new drugs across the genetic spectrum. For every cancer patient, time is of the utmost importance. In the future, colorectal cancer patients could get faster access to treatments working for breast or lung cancer." 

The Study that Changed it All

The approval was based on data from 149 patients with MSI-H or dMMR cancers enrolled across 5 single-arm clinical trials. 90% of those patients had colorectal cancer. Nearly 40% of those enrolled showed a significant reduction in tumor size, including including 11 (7.4%) complete responses and 48 (32.2%) partial responses. Side effects included fatigue and diarrhea. Keytruda is the first drug of its kind to work in colon cancer. It is monoclonal antibody, which uses a patient’s own cells to kill cancer by enabling the body’s natural immune response to tumor cells. The catch is, however, this drug is only effective for a small group of patients. Only about 5% of patients with metastatic colorectal cancer have MSI-H or dMMR tumors. “The FDA approval of Keytruda is a perfect example of why participating in clinical trials is so important and how researchers, doctors, patients and the medical community can work together to find better, targeted treatments based on genomics," Sapienza continued. "Tools like our new Clinical Trials Finder, which matches patients based on stage, location and even biomarker, connect patients to studies their doctor may not even know to recommend. This breakthrough would never have been possible without the courage of those patients willing to participate in the future of cancer research.”

What does it mean to have MSI-H?

MSI stands for microsatellite instability. If you remember from high school biology class, the human body has hundreds of thousands of cells that are dividing and multiplying at any given time. Each time a cell divides, its DNA is copied from the old cell to the new cell. Normally, the DNA in the new cell is identical to the DNA in the old cell, but occasionally, the cell doesn’t quite get the copy correct and a small section of the DNA (also known as a microsatellite) has a small error and doesn’t quite match the original. In any person, these errors are normal and the human body is designed with a built-in mechanism to naturally fix these mismatches. However, if you are MSI-high, your body has a deficiency in the mismatch repair mechanism. In the case of Keytruda, being MSI-high is great news, as it means you will be a great candidate for the drug.