Clinical harm from failure to deploy personalized medicine for patients with metastatic non–small cell lung cancer

BACKGROUND: Among the estimated 234,580 patients diagnosed with lung or bronchus cancer in 2024, an estimated 66%, or 154,823 patients, were diagnosed with advanced or metastatic non-small cell lung cancer (mNSCLC). More than half of patients have a genomic variant that can be treated with targeted therapy. Despite widespread evidence supporting the survival benefits of biomarker-driven management of patients with mNSCLC, real-world implementation of precision oncology has not kept pace with recommendations. OBJECTIVE: To quantify the potential survival deficit from underutilization of precision oncology (genomic testing and matched therapy) for patients with newly diagnosed mNSCLC in the United States. METHODS: We developed a simulation model comparing Observed Practice with Optimal Practice in which all eligible patients receive biomarker testing and appropriate treatment. We assessed a mix of 3 testing pathways assessed: (1) guideline-concordant biomarker testing consistent with National Comprehensive Cancer Network (NCCN) Guideline recommendations, (2) nonguideline biomarker testing, and (3) no biomarker testing. Input values and probabilities for each pathway were obtained from published data. Survival deficit was estimated as life-years lost in Observed Practice vs Optimal Practice. RESULTS: Among the estimated 92,401 patients with new metastatic adenocarcinoma or large cell carcinoma histology, 49,427 patients were projected to have at least 1 of the 10 NCCN-recommended mutations with a known targeted first-line therapy. Among those harboring actionable mutations, 46,757 were assumed to be identified and treated with precision-matched targeted therapy (PMTT) in Optimal Practice vs 28,177 in Observed Practice. The 46,757 patients receiving PMTT in Optimal Practice realized a total of 113,417 life-years, a gain of 20,901 over the patients treated in Observed Practice. CONCLUSIONS: Among patients with mNSCLC in the United States, suboptimal use of recommended panel testing and implementation of precision medicine for newly diagnosed mNSCLC is associated with life-years lost. Investments in effective programs that improve adherence to NCCN guideline recommendations and test-concordant therapy would result in increased life expectancy for up to 20,000 patients annually.