Dr. Vokes on Investigative Biomarkers of Response to Checkpoint Inhibitors in Cancer

Natalie I. U. Vokes, MD, a medical oncologist fellow at Dana-Farber Cancer Institute, discusses investigative biomarkers of response to checkpoint inhibitors in the field of oncology.

Tumor mutational burden is the most well-developed biomarker in the field of oncology, says Vokes. Many of the early studies that used whole exome sequencing and looked for genomic correlates noted that TMB in patients who responded to treatment is often higher than in those who do not respond.

This was initially demonstrated in studies that used whole exome sequencing in melanoma and has since been confirmed via a number of different sequencing techniques in an array of disease contexts. There has been a lot of interest in further developing TMB as a biomarker.

Other biomarkers are not as well developed, adds Vokes. For example, in lung cancer, 1 biomarker that comes up quite a bit are STK11 mutations; this is generally a poor prognostic marker across different treatment settings, Vokes adds. There is also some work showing the presence or absence of other comutations, such as TP53 or KRAS informs how detrimental the STK11 mutation is. There is a lot that the field still has to learn in that regard, says Vokes.

In lung cancer, the use of driver mutations as biomarkers, such as EGFR, ALK, or ROS1, are taken for granted, she adds. Those patients tend to not respond as well to treatment, but 1 should be cautious that this is not extended to all driver alterations in non–small cell lung cancer. This is because mutations such as BRAF and MET might be biologically different. The field is still learning about these other biomarkers and stronger understanding is anticipated over the next couple of years, concludes Vokes.