Dr Malla on the Impact of Specific Biomarkers in First-Line Treatment Selection for GI Cancers

“[The impact of each biomarker on first-line treatment selection] is an extremely important question, GI cancers are now a collection of biomarker-defined diseases.”

Midhun Malla, MD, an associate professor of medicine, hematology and Oncology at the University of Alabama at Birmingham discussed biomarkers such as HER2, KRAS, and FGFR in gastrointestinal (GI) cancers. In addition to discussing each of these biomarkers, Malla discussed how they each effect first-line treatment selection for patients with GI cancers. Malla also covered circulating tumor DNA (ctDNA) testing in GI cancers today, and future improvements to be made that may increase its utility in the field.

Malla began by asserting that GI cancers are now classified as a collection of diseases that are defined by biomarkers, contrasting from how they were defined in the past. Regarding, tumor-focused biomarkers, he looked to RAF-and RAS-mutation status, BRAF V600E, as biomarkers specifically relevant for colorectal cancers in the frontline space. Malla also highlighted KRAS G12Ctargeting plus anti-EGFR therapies as potential biomarker-driven frontline approaches. The variety of biomarkers and biomarker-driven approaches developing in the frontline setting across GI cancers make it an exciting time in the field, he added.

Malla transitioned to discussing the role of ctDNA, noting that the tool is not only exciting in GI cancers but across multiple cancer types. Gene sequencing, measuring minimal residual disease (MRD), surveillance, and immunotherapy response monitoring were all utilities that help make ctDNA useful in GI cancers, Malla said. He also underscored how ctDNA testing helps monitor resistance in patients, like those with wild-type RAS. In terms of de-escalation, Malla pointed out how utilizing ctDNA to measure MRD can help oncologists identify which patients to de-escalate toxic therapies like chemotherapy.

Malla concluded by touching on the current limitations of ctDNA in GI cancers, specifically, verifying results and acting on them. Both negative and positive tests are possible with ctDNA depending on the context, Malla emphasized, therefore ensuring ctDNA is being used in the right situations and evaluated multiple times is crucial. Moreover, Malla discussed how acting on positive-MRD test results via ctDNA have not yet been proved to improve outcomes like disease-free survival in patients.