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We recently hosted a webinar called “Optimizing NSCLC Treatment with Biomarker Testing Insights”, featuring Dr. Jessica Lin of Mass General Cancer Center. In it, Dr. Lin discussed how biomarker testing identifies genetic mutations and resistance mechanisms in non-small cell lung treatment, informs better treatment decisions, and influences patient care. Listen to the replay and learn about the latest advancements that are transforming NSCLC treatment and driving improved patient outcomes.
**A summary of the discussion is below**
In lung cancer treatment, genetic mutations, or biomarkers, play a crucial role in customizing therapies that target specific characteristics of each patient’s tumor. Here, we’ll explore several important biomarkers for non-small cell lung cancer (NSCLC), the treatment options available for each, and why biomarker testing is key to accessing clinical trials and advanced therapies.
Key Biomarkers in Lung Cancer
EGFR Mutations: Found in 10-15% of NSCLC cases, EGFR mutations have targeted therapies that can inhibit cancer growth. These mutations are pivotal in determining eligibility for EGFR-targeted treatments, particularly post-surgical therapies.
ALK Rearrangements: Present in 3-5% of NSCLC cases, ALK gene alterations are often treated with ALK inhibitors such as lorlatinib. Postoperative ALK-targeted therapies are also available to prevent recurrence in surgically resected cases.
ROS1 and RET Rearrangements: Occurring in 1-2% of patients, these gene alterations allow for targeted therapies that effectively address ROS1 and RET-driven cancers.
MET Exon 14 Skipping Mutations: Detected in 2-4% of cases, this mutation activates the MET protein, enhancing cancer cell survival. Targeted MET inhibitors, such as capmatinib and tepotinib, are approved for this mutation and have shown substantial effectiveness.
KRAS Mutations: KRAS mutations are among the most common in lung cancer, particularly the KRAS G12C mutation. While once considered “undruggable,” advancements now offer targeted therapies for this mutation, and clinical trials are rapidly expanding to cover other KRAS variants.
HER2 Mutations: Present in 2-3% of NSCLC cases, HER2 mutations can also be treated with targeted therapies, with further research ongoing to optimize treatment strategies.
Emerging Biomarkers and Future Directions
New and emerging biomarkers, such as NRG1 fusions and MET amplifications, show promising response rates to targeted therapies currently in clinical trials. MET amplification, for example, can activate cancer pathways similar to MET exon skipping mutations, and targeted inhibitors for these alterations are being explored in trials.
KRAS and other biomarkers that once lacked treatment options now benefit from an expanding array of targeted therapies, underscoring the rapid evolution of precision medicine in lung cancer.
Why Biomarker Testing Matters
Comprehensive biomarker testing enables a precise diagnosis, guiding doctors to the most effective FDA-approved treatments and opening up access to promising clinical trials. Broad panel testing, typically via next-generation sequencing (NGS), identifies a wide range of gene alterations. This testing is crucial, as many biomarker-driven therapies and trials may not be available universally, and treatments vary between centers.
Clinical Trials and New Treatment Opportunities
For each biomarker, numerous clinical trials are underway to explore innovative treatment options. Biomarker testing not only directs patients to the most suitable standard treatments but also provides access to cutting-edge trials and therapies that may not yet be FDA-approved. Seeking second opinions and consulting with specialized centers can be essential in accessing these opportunities.
Immunotherapy and PD-L1 Levels
PD-L1 expression levels also inform treatment choices in NSCLC. When PD-L1 expression is low (<1%), immunotherapy alone may be less effective, often leading doctors to recommend a combination with chemotherapy. For early-stage, surgically resected lung cancers, checking for EGFR and ALK mutations is essential, as specific targeted therapies can reduce recurrence risk.
The Bottom Line
For NSCLC patients, understanding their tumor’s unique genetic makeup is essential for tailoring treatments. As research advances, biomarker-driven therapies continue to expand, offering hope and options beyond traditional methods. With comprehensive biomarker testing and access to clinical trials, patients benefit from a more targeted, personalized approach to lung cancer treatment, significantly improving outcomes and quality of life.
