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

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?

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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 explores the critical decision-making process for selecting between osimertinib monotherapy and combination therapy approaches for patients with EGFR-mutant metastatic non–small cell lung cancer (mNSCLC). The discussion emphasizes that treatment selection depends heavily on patient-specific factors rather than universal protocols. For patients with straightforward EGFR mutations without concerning comutations or resistance mechanisms, clinicians engage in detailed discussions about available data and treatment options, treating their role as helping patients “choose from a menu of things.”

Patient demographics and clinical characteristics play crucial roles in treatment selection. Frail, older patients and those with significant comorbidities that make them poor candidates for infusional therapy or at high risk for severe adverse effects are often considered for monotherapy approaches. However, the panel emphasizes that age alone should not be a determining factor—rather, the patient’s willingness to pursue aggressive treatment and their individual preferences are paramount. The approach involves tailoring treatment not only to disease biology but also to patient values and goals of care.

Regarding combination therapy selection, the panel reveals practical implementation challenges and preferences. While both osimertinib plus chemotherapy and amivantamab plus lazertinib are available options, some centers have primarily utilized osimertinib plus chemotherapy in the frontline setting rather than the amivantamab combination. Patient performance status and medical robustness significantly influence treatment recommendations. The discussion highlights the importance of shared decision-making, particularly given the incurable nature of metastatic disease. Quality of life considerations become paramount in these discussions, as patients must weigh the potential benefits of more aggressive combination approaches against the impact on their day-to-day well-being and treatment convenience.