8621 Background: Amivantamab plus lazertinib and osimertinib plus chemotherapy are guideline-recommended first-line treatment options for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletion or exon 21 L858R mutations. Although both treatments are first-line options, their relative economic value has not been evaluated. This study evaluated the cost-effectiveness of amivantamab plus lazertinib versus osimertinib plus chemotherapy from a United States payer perspective. Methods: A partitioned survival model (PSM) and a three-state Markov model were developed to compare the two treatment strategies over a lifetime horizon. Clinical efficacy inputs were derived from the MARIPOSA and FLAURA2 trials. Direct medical costs and health state utilities were obtained from published sources. Outcomes included total costs, life years (LYs), and quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were conducted to assess model robustness using a willingness-to-pay threshold of 150, 000 per QALY or LY gained. Results: Across both modeling approaches, osimertinib plus chemotherapy was associated with greater effectiveness and lower costs compared with amivantamab plus lazertinib. In the partitioned survival model, osimertinib plus chemotherapy resulted in 1. 68 additional QALYs and 2. 18 additional LYs with cost savings of 34, 799, indicating dominance. Similar findings were observed in the Markov model, with gains of 2. 05 QALYs and 2. 74 LYs and cost savings of 46, 620. Sensitivity analyses identified survival extrapolation parameters and the discount rate as the primary drivers of uncertainty. In probabilistic sensitivity analysis, osimertinib plus chemotherapy was favored in approximately 82% of simulations. Conclusions: From the United States perspective, osimertinib plus chemotherapy was dominant over amivantamab plus lazertinib as first-line treatment for EGFR-mutated advanced NSCLC in this model-based economic evaluation. These findings highlight the importance of integrating clinical efficacy and economic value in first-line treatment selection. Future studies should compare all recommended first-line strategies using mature survival data and incorporate real-world treatment patterns and patient-centered outcomes. Base case results. Regimen Total Costs Total QALYs Total LYs Δ Cost Δ QALYs Δ LYs ICER (Cost/QALY) ICER (Cost/LY) Partitioned Survival Model Amivantamab + Lazertinib 1, 297, 932 3. 23 4. 65 - - - - - Osimertinib + Chemotherapy 1, 263, 133 4. 91 6. 83 -34, 799 1. 68 2. 18 Dominant Dominant Markov Model Amivantamab + Lazertinib 1, 311, 688 2. 76 3. 97 - - - - - Osimertinib + Chemotherapy 1, 265, 068 4. 81 6. 71 -46, 620 2. 05 2. 74 Dominant Dominant
Gokhale et al. (Thu,) studied this question.