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RET Aberrations and EGFR Exon 20 Insertions Testing in the Complex NSCLC Biomarker Landscape

In his recent OncomineWorld webinar, Dr. Fernando López-Ríos, MD, PhD
(Department of Pathology, 12 de Octubre” University Hospital, Madrid, Spain)
described the latest developments and challenges in the complex NSCLC biomarker landscape, explaining why frontline next-generation sequencing (NGS) is crucial to advance progress.

Dr. Fernando López-Ríos, MD, PhD
Department of Pathology, 12 de Octubre”
University Hospital, Madrid, Spain


Recommendations for Routine Biomarker Testing in NSCLC

With the ever-increasing number of NSCLC biomarkers and the speed of targeted treatment innovation, testing guidelines are quickly expanding while labs scramble to keep pace. Dr. López-Ríos highlighted the European Society for Medical Oncology (ESMO) recommendations for the routine use of NGS on tumor samples for advanced NSCLC, as well as the National Comprehensive Cancer Network (NCCN) guidelines for broad molecular profiling of EGFR, ALK, KRAD, ROS1, BRAF, NTRK1/2/3, MET ex14 skipping, and PD-L1. Simultaneous NGS profiling of thousands of alterations delivers comprehensive information at high specificity and sensitivity to inform precision medicine.

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Next, Dr. López-Ríos focused on EGFR exon 20 insertions and RET fusions as some of the latest biomarkers for routine NGS testing in NSCLC.

EGFR exon 20 insertions and RET fusions traditional testing challenges

  • PCR methods miss > 50% of exon 20 insertions due to heterogeneity
  • RNA-based multiplex assays can miss some RET fusions


Taking a page from SR Covey’s The 7 Habits of Highly Effective People, Dr. López-Ríos presented a multi-step action plan to help labs achieve highly effective biomarker testing.

All patients with NSCLC should have the opportunity to benefit from appropriate targeted therapies—as more labs leverage the power and speed of NGS, more patients will.

Recognizing the daily challenges of mixed testing modalities, Dr. López-Ríos suggested that labs synergize their efforts through creative cooperation and optimizing their work and communication flows. He reviewed CAP, IALC, AMP, and ASCO recommendations “that unexpected, discordant, equivocal, or otherwise low confidence test results be confirmed with an alternative method or sample”.

Dr. López-Ríos offered suggestions on how labs can achieve fast biomarker results with weekly planning, daily action, and streamlined teamwork.

Make it a Win-Win
Dr. López-Ríos recommends that labs create joint-force molecular tumor boards to integrate clinical, pathology, and biomarker data, analyze current literature, and troubleshoot molecular redundancy and driver negative patients. He shared data that his molecular tumor board strategy can improve outcomes.



Single gene testing will continue to coexist with broader molecular profiling, but fast, reliable NGS testing has become imperative.

NGS testing for RET fusions and rare EGFR mutations now can be considered as the standard of care, and the number of actionable biomarkers is ever-increasing. Dr. López-Ríos concluded that it’s time for labs to implement NGS as frontline biomarker testing in NSCLC.

Learn more by watching Dr. López-Ríos full presentation.


For Research Use Only. Not for use in diagnostic procedures.


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Thermo Fisher Scientific Staff
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