Welcome to OncLive On Air®! I’m your host today, Courtney Flaherty.

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, Michael J. Pishvaian, MD, PhD, sat down to discuss the evolving role of biomarker-directed strategies in gastrointestinal (GI) oncology, as well as the importance of early comprehensive testing to identify molecular drivers and resistance mechanisms when approaching frontline treatment selection and sequencing.

Pishvaian serves as director of the Gastrointestinal, Developmental Therapeutics, and Clinical Research Programs for the Johns Hopkins Kimmel Cancer Center in the National Capital Region.

Pishvaian began the discussion by highlighting the shift from a disease-site-specific approach to a molecularly defined paradigm, noting that microsatellite instability–high status and NTRK fusions now dictate therapy regardless of tumor origin. He reviewed the transformational data from the phase 3 HERIZON-GE-01 trial (NCT04276493), positing that zanidatamab (Ziihera) could become the new standard of care for HER2-positive upper GI cancers due to unprecedented survival outcomes. He also emphasized the emergence of Claudin 18.2-directed therapies, noting that data from the phase 2 ILUSTRO study (NCT03505320) demonstrates remarkable progression-free survival when adding zolbetuximab (Vyloy) to mFOLFOX6 and nivolumab (Opdivo) for high-expressing subgroups.

The conversation then shifted to colorectal cancer, where Dr. Pishvaian detailed how data from the phase 3 BREAKWATER trial (NCT03845036) has "locked in" a paradigm requiring frontline testing for BRAF V600E mutations to guide the use of encorafenib (Braftovi) plus cetuximab (Erbitux). He also discussed the "care revolution" in KRAS inhibition, spotlighting the significant survival benefits seen with daraxonrasib in pancreatic cancer and the potential for novel allele-specific inhibitors to combat disease resistance.

Finally, Pishvaian addressed the practicalities of implementation, noting that testing rates in the community remain low. He advocated for prioritizing testing, including liquid biopsies and ctDNA, at the time of initial diagnosis to ensure no patient is left behind.

This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.