Continuing the Targeted TKI in the Second Line for the Treatment of EGFR-Mutant NSCLC
Panelists discuss how the decision to continue targeted TKI therapy in the second-line setting depends on multiple factors including intracranial progression status, extent of disease progression, prior radiation therapy, and individual patient circumstances, with clinicians preferring to continue TKI for isolated CNS progression that can be managed with radiation while switching to different regimens for widespread progression or recurrent intracranial disease after prior radiation.
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
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 addresses the complex decision-making process regarding continuation of targeted tyrosine kinase inhibitors (TKIs) in second-line treatment for EGFR-mutant metastatic non–small cell lung cancer (NSCLC) following disease progression. The discussion reveals this as a controversial topic without a one-size-fits-all approach, requiring individualized assessment based on multiple clinical factors. The primary consideration involves evaluating intracranial progression status, as patients without brain involvement during frontline therapy are more likely candidates for TKI continuation. The availability of local radiation therapy for oligoprogressive disease also influences the decision, with successful local control supporting continued TKI use rather than complete regimen changes.
The clinical approach emphasizes comprehensive disease assessment including extent and pattern of progression. For patients experiencing their first intracranial progression event, the decision depends on whether progression is limited to the brain or involves widespread extracranial disease. Oligometastatic intracranial progression often warrants stereotactic radiosurgery with continued TKI therapy, while extensive multisystem progression typically prompts complete treatment regimen changes. For patients who have already received brain radiation and experience subsequent intracranial progression, transitioning to entirely different regimens becomes more appropriate. Alternative strategies include dose escalation studies examining higher osimertinib doses (160 mg vs 80 mg), particularly for patients with limited options or leptomeningeal disease where increased central nervous system (CNS) penetration may provide temporary benefit.
The fundamental question underlying these decisions involves assessing continued TKI efficacy and the subjective clinical judgment of whether the drug is still providing meaningful disease control. The definition of treatment failure has evolved significantly, particularly regarding CNS progression patterns and blood-brain barrier considerations. The 2025 treatment landscape offers more nuanced approaches to progression compared with previous eras, requiring case-by-case evaluation that balances continued targeted therapy benefits against the need for complete treatment paradigm shifts when disease biology has fundamentally changed.
