Deciding Between a Biomarker-Directed Approach and a Biomarker-Agnostic Approach for Second-Line Treatment of EGFR-Mutant NSCLC

EP: 1.The Evolution of EGFR-Mutated Advanced NSCLC Treatment: Present Considerations and Future Treatment Options

EP: 2.Has Combination Therapy Become the New Frontline Treatment Standard for EGFR-Mutant Metastatic NSCLC?

EP: 3.Decision Points to Consider When Choosing Treatment With Monotherapy or Combination Therapy for EGFR-Mutant mNSCLC

EP: 4.Evaluating Patient Preferences for the Treatment of EGFR-Mutant mNSCLC

EP: 5.Comparing the Combination Therapies for the Treatment of EGFR-Mutant mNSCLC

EP: 6.Considering Resistance Mechanisms When Choosing Therapy in the Frontline Setting

EP: 7.The Importance of Maintaining Quality of Life and Intervening Early When Adverse Events Occur in the Frontline Treatment Setting

EP: 8.Weighing the 1-Year Projected Overall Survival Benefit With MARIPOSA in the Frontline Treatment of EGFR-Mutant mNSCLC

EP: 9.Discussing the Time and Financial Toxicities Associated With Combination Therapies and Potential Mitigation Strategies

EP: 10.Discussing Potential Combination Therapy Medication-Associated Toxicities With Patients

EP: 11.Evaluating the Clinical Utility of Subcutaneous Amivantamab in the Treatment of EGFR-Mutant mNSCLC

EP: 12.The Importance of Multidisciplinary Collaboration With Subspecialty Physicians in the Toxicity Management With Treatment

EP: 13.Exploring Second-Line Treatment Options Including Targeted Radiation and Surgery for the Management of EGFR-Mutant mNSCLC

EP: 14.Tissue vs Plasma Biopsy After First Disease Progression in EGFR-Mutant NSCLC

Now Viewing

EP: 15.Deciding Between a Biomarker-Directed Approach and a Biomarker-Agnostic Approach for Second-Line Treatment of EGFR-Mutant NSCLC

EP: 16.Continuing the Targeted TKI in the Second Line for the Treatment of EGFR-Mutant NSCLC

EP: 17.When to Consider Retreatment With Chemotherapy After FLAURA2 for EGFR-Mutant NSCLC

EP: 18.Patient Case Presentation: A 45-Year-Old With Newly Diagnosed EGFR-Mutant mNSCLC and Liver Metastases

EP: 19.Patient Case Presentation: A 69-Year-Old With Newly Diagnosed EGFR-Mutant mNSCLC and Symptomatic Brain Metastases

This segment explores the strategic decision-making process between biomarker-directed and biomarker-agnostic approaches for second-line treatment of EGFR-mutant metastatic non–small cell lung cancer (NSCLC). The discussion occurs in the context of expanding treatment options, including the recent availability of trastuzumab deruxtecan for EGFR-mutant disease and the potential for chemotherapy as a treatment class depending on frontline therapy choices. The panel addresses how clinicians prioritize between targeted therapies that require specific biomarkers vs broader approaches that don’t depend on molecular alterations.

The preferred clinical approach emphasizes exhausting all available targeted therapy options before transitioning to biomarker-agnostic treatments. This strategy prioritizes maximizing the use of precision medicine approaches, such as utilizing amivantamab in the second-line setting if it wasn’t used in the front line, and targeting specific resistance alterations identified through molecular testing. Only after depleting targeted options do clinicians consider biomarker-agnostic approaches like trastuzumab deruxtecan or docetaxel. This sequential approach reflects the principle that targeted therapies typically offer superior efficacy and tolerability profiles when appropriate molecular targets are present.

The implementation of this strategy requires comprehensive molecular profiling at disease progression, with increased utilization of plasma-based testing for patients experiencing disease progression. The decision-making process considers patient fitness for tissue rebiopsy, patient preferences regarding invasive procedures, and the potential for identifying actionable molecular alterations that could guide targeted therapy selection. Clinical teams are systematically reviewing molecular testing reports before initiating second-line therapy to ensure optimal treatment matching. This approach represents a commitment to personalized medicine principles, where the goal is to match each patient with the most appropriate targeted therapy based on their specific molecular profile before considering broader treatment approaches that don’t require specific biomarkers for efficacy.