Agnostic savior.

The FDA made news recently by approving Keytruda (pembrolizumab, a PD-1 inhibitor) for any tumor with microsatellite instability (MSI) or mismatch repair (MMR) deficiency. This is the first time a cancer drug approval is not linked to a specific histology or tumor site, a so-called agnostic indication. This goes back to early Keytruda data initially reporting poor responses in colon cancer. Further exploration revealed there actually were responders if you looked just at those with MSI or MMR defects. Compiling data among these populations from multiple trials showed a response rate of 40%, with 80% of those having durable responses of >6 months...thus the agnostic indication. Why MSI/MMR? Their genomic instability is thought to create lots of antigens and intense immune infiltrate. Tumors normally use the PD-1 axis to go under-cover in the presence of this infiltrate, but blocking PD-1 unmasks these cells and it's game on.


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