Gaps and Future Directions in NSCLC Biomarker Testing: Liquid Biopsy, MRD, and Non-Actionable Alterations

Dr. Singhi opens by asking Dr. Jani to identify the greatest unmet needs in biomarker-driven NSCLC care and how strategies may evolve, including repeat liquid biopsies and integrating complex genomic patterns into decision-making.

Dr. Jani identifies the biggest challenge as patients with non-actionable alterations. He notes that while newer TKIs for EGFR, ALK, and ROS are achieving progression-free survival exceeding 40–50 months, patients lacking established targets have had fewer options—though KRAS and HER2 are now entering the actionable space with frontline clinical trials. He highlights liquid biopsy as a key tool for tracking how tumor biology evolves under treatment, emphasizing that both ctDNA and ctRNA are valuable, ctRNA in particular, for capturing fusion data and identifying resistance alterations. He also discusses the potential of MRD testing and VAF-based therapeutic monitoring, while acknowledging that clinical guidance on how to act on these data remains limited and individualized.

Dr. Singhi adds that incomplete biomarker testing remains a significant barrier, noting that real-world data show only about three-quarters of stage IV patients receive full NGS testing. Dr. Jani responds that emerging data support switching to targeted therapy even after chemoimmunotherapy has been started, if an actionable alteration is identified, reinforcing the importance of testing at any point in the treatment course.

In the next episode, "Final Remarks and Closing: Biomarker-Driven Management in NSCLC," the experts summarize key takeaways and reinforce the role of comprehensive testing in optimizing patient outcomes.