2017: Cancer Therapy by Biomarker

On This Day in Health: May 23, 2017

On May 23, 2017, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab, sold as Keytruda, for certain solid tumors with specific biological features. The decision was the first FDA cancer-treatment approval based on a tumor biomarker rather than the place in the body where the cancer began. It covered microsatellite instability-high or mismatch repair-deficient tumors, commonly shortened to MSI-H and dMMR, with conditions concerning advanced disease and previous treatment. This was a change in how an indication could be defined. It did not mean that every cancer could receive the medicine or that the organ of origin had stopped mattering.

Mismatch repair is a cellular process that helps correct mistakes made when DNA is copied. When that repair system is deficient, errors can accumulate. Microsatellite instability describes changes in short repeated DNA sequences associated with that problem. These tumor features can help identify cancers that may be more susceptible to immune checkpoint treatment. Pembrolizumab does not repair the DNA defect itself. It acts on the immune system by blocking PD-1, a checkpoint that can limit immune activity. The biomarker helped identify a treatment opportunity even though it was not the direct target of the antibody. That distinction is central to the scientific meaning of the approval.

The initial evidence combined five clinical trials involving 149 patients across several cancer types. Researchers examined tumor response and how long the benefit persisted, rather than conducting a single study restricted to one organ. The accelerated pathway allowed the decision to proceed on that evidence while requiring additional work. Some patients responded, and others did not. Serious immune-related inflammation also remained a concern because a treatment that increases immune activity can affect healthy organs. The original indication contained specific requirements for prior treatment, including separate wording for colorectal cancer. Those details were part of the approval, so its historic breadth should not be mistaken for an unrestricted authorization.

May 23 provided a concrete example of a different way to organize cancer care. A shared biological feature could connect tumors that had previously been considered through separate organ-specific categories. For a patient with few remaining options, that connection could open a treatment discussion that otherwise might not occur. It also increased the importance of obtaining and interpreting the relevant test result. The milestone is best remembered as a precise expansion of possibility: evidence supported use across several tumor types when a qualifying biomarker and the other clinical conditions were present. The achievement changed the framework of an approval while preserving the need for individual assessment, careful monitoring and further research.