EGFR Exon 19 Deletion NSCLC With MET Amplification and TP53 Mutation: What Is the Optimal First-Line Approach?

A 72-year-old man with a history of tobacco use, controlled hypertension, and mild chronic kidney disease presented with symptoms including shortness of breath, fatigue, and significant weight loss. Imaging revealed an extensive disease burden characterized by a dominant left lower lobe lung mass, diffuse bilateral lung nodules, and multifocal liver and bone metastases, but no brain involvement. Molecular profiling identified an EGFR exon 19 deletion, along with a TP53 mutation and MET amplification. Despite his age and comorbidities, the patient maintains a good quality of life and wishes to extend survival as long as possible. The clinical dilemma centers on whether to pursue monotherapy or combination therapy for this high-risk patient.

Although the patient’s age and comorbidities might initially suggest monotherapy as a safer option, the significant disease burden and high-risk molecular features, including MET amplification and TP53 mutation, indicate a more aggressive approach may be warranted. The presence of symptomatic, multifocal disease affecting the liver and bones supports the consideration of combination therapy. One combination regimen discussed was the MARIPOSA trial approach, which includes targeted therapies alongside chemotherapy. However, kidney function and chemotherapy tolerability must be carefully weighed, especially in older patients with mild renal impairment.

Patient preferences and goals of care are paramount in guiding treatment decisions. Although many patients initially express a desire to prolong life as much as possible, deeper conversations often reveal a more nuanced balance between survival and quality of life. For some, monotherapy may be appropriate to preserve day-to-day well-being, especially if they prioritize symptom control and avoiding treatment-related toxicity. In this case, given the patient’s expressed desire for aggressive care and the high-risk features, combination therapy remains the favored option, though individualization of treatment based on ongoing patient dialogue is essential.