publication date: Oct. 13, 2017

The genesis of the first site-agnostic indication

By Paul Goldberg

When he was at Johns Hopkins, there was nothing whatsoever noteworthy about Luis Diaz wandering into Bert Vogelstein’s office.

Usually, an idea—sometimes even a good idea—was involved.

The idea Diaz brought in one day five years ago was clearly one of the good ones:

“I said, ‘Bert, I think I know how these things work,’” Diaz said. The “things” Diaz was referring to were PD-1 and PD-L1 drugs, also known as checkpoint inhibitors. “They respond in melanoma and lung cancer, and I think it’s high mutation.”

LuisDiaz

Luis Diaz, then at Johns Hopkins, had a hunch that resulted in the first site-agnostic approval in history.

It might then follow that microsatellite instability-high colorectal cancers would be more likely to respond to checkpoint inhibitors. This might apply to hereditary MSI-H, found in the Lynch syndrome, the molecular basis for which Vogelstein helped define, as well as sporadic MSI-H. Vogelstein is the Clayton Professor of Oncology and Pathology and director of the Ludwig Center for Cancer Genetics and Therapeutics at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

A clinical trial in the MSI-H or dMMR population could thus provide a treatment option for a subset of colorectal cancer patients—and it could predict which patients are likely to benefit from these drugs in other sites. Perhaps, this could lay the groundwork for … Continue reading The genesis of the first site-agnostic indication

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