Comparing the Combination Therapies for the Treatment of 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?

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

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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 focuses on the practical considerations when choosing between 2 combination therapy approaches for EGFR-mutant metastatic non–small cell lung cancer (mNSCLC): osimertinib plus chemotherapy vs amivantamab plus lazertinib. The discussion reveals that many oncology practices have gravitated toward the chemotherapy plus osimertinib combination, viewing it as pairing 2 familiar therapeutic components together. In contrast, the amivantamab and lazertinib combination, while containing medications that clinicians have used before, represents a somewhat more intimidating option for both patients and providers due to its novelty as a paired regimen.

The panel addresses practical implementation strategies that differ from clinical trial protocols. While the amivantamab and lazertinib studies aimed to maintain patients on both therapies for as long as possible, real-world practice allows for more flexible approaches. Clinicians report having a “quicker trigger” to discontinue chemotherapy, particularly in patients demonstrating good early responses. This approach acknowledges that chemotherapy works faster but may not be as durable, allowing for treatment modification based on individual patient responses. Some practitioners may discontinue pemetrexed maintenance therapy in patients who are doing well and prefer to avoid the inconvenience of infusion visits every 3 weeks.

The discussion emphasizes the value of having multiple mechanistic approaches available for targeting EGFR-mutant disease. Until definitive evidence emerges regarding which combination approach is superior as initial therapy, having different mechanistic strategies provides important sequencing flexibility. This variety allows clinicians to potentially reserve alternative approaches for later lines of therapy, maximizing treatment options throughout the patient’s disease course. The availability of distinct combination strategies represents a strategic advantage in managing a complex disease where resistance mechanisms may eventually emerge, ensuring that patients have access to different therapeutic pathways as their treatment needs evolve over time.