A cost-effectiveness analysis model of actionable genomic alteration testing strategies incorporating different modalities and sizes of next-generation sequencing panels in non-small-cell lung cancer.

Background: Prompt identification of actionable genomic alterations (AGAs) is essential in guiding treatment decisions in newly diagnosed advanced non-small-cell lung cancer (NSCLC). Objectives: We aimed to determine the optimal testing strategy in terms of proportion of AGAs detected, time-to-treatment decision (TTTD) and average costs/patient in Singapore, a high-frequency AGA population. Design: A model was constructed to evaluate AGA testing strategies, comparing the cost-effectiveness and budget impact of each strategy. Methods: The 24 strategies studies included (1) upfront tissue/plasma next-generation sequencing (NGS) alone (small/medium/large panel), (2) exclusionary tissue single-gene testing (EGFR, ALK and ROS1) followed by tissue/plasma NGS, (3) exclusionary plasma EGFR followed by tissue or plasma NGS, (4) sequential single-gene testing followed by tissue/plasma NGS, (5) exclusionary or sequential testing without NGS and (6) small panel tissue NGS with fluorescence in situ hybridization (FISH) for ALK, ROS1, RET and MET. Literature review was performed to determine the incidence of NSCLC and the prevalence of each AGA in the population; costs, gene coverage and turnaround times were sourced through market research. Results: AGAs and EGFR mutations occurred in 76.7% and 56.0% of patients, respectively. Upfront medium panel tissue NGS detected all AGAs at USD1813/patient, with a TTTD of 7 days-no benefit was seen from using large panel tissue NGS at a higher cost. Exclusionary tissue testing followed by medium panel tissue NGS detected 98.9% of AGAs at USD1506/patient, with a TTTD of 14.9 days. Exclusionary plasma EGFR testing followed by medium panel tissue NGS detected 98.3% of AGAs at USD1047/patient, with a TTTD of 8.4 days. Upfront small panel tissue NGS with FISH also detected 98.3% of AGAs at a cost of USD798/patient, with a TTTD of 14 days. Conclusion: In our high EGFR-mutation prevalence population, exclusionary plasma EGFR followed by medium panel tissue NGS was cost-effective. Our analysis provides insight on NGS testing strategies of different gene panel sizes and sample types.