David Fabrizio Discusses Challenges of Biomarker-Driven Cancer Treatment

The use of biomarkers in immunotherapy has some technical and biological limitations, and is complicated further by the qualitative aspect of cancer treatment, said David Fabrizio, of Foundation Medicine, Inc. A genomic-based solution could help develop more unified quantitative approaches.

Transcript (slightly modified)

Does biomarker-driven treatment remain a challenge with checkpoint inhibitors?

Yes, absolutely. I think a resounding absolutely. Our first crack at biomarkers in immunotherapy has been protein-based expression and immunohistochemistry staining, and although this does have clinical utility, there are quite a number of limitations associated with that. Some of those limitations are explained by technical aspects of that assay and biological limitations of simply looking at protein-based expression.

But I think at the end of the day, what it comes down to is that the score that you determine based on that type of assay, there’s always a human element associated with that, so there’s a qualitative aspect to it. That qualitative aspect of determining percent positivity, essentially, makes it difficult to adopt as sort of standard best practice. I think, because of that, we need more unified quantitative approaches.

We see the solution there as a genomic-based solution, and so we’ve done that through the emergence of a biomarker we call tumor mutational burden or TMB, which is really just a measure of the number of somatic mutations that exist in a patient’s cancer genome. And we’ve shown, across a number of indications actually, that TMB has quite effective clinical utility at stratifying those who actually benefit, respond, and survive longer versus those who don’t.