Abstract 1299: Cost-effectiveness analysis of circulating tumor DNA-based molecular profiling platforms for the detection of EGFR mutations in lung cancer
Authors: Rozendal Pim , van der Leest Paul , van der Logt Elise M. , Rifaela Naomi , Platteel Inge , Scherpen Frank J. , Groen Harry J. , van Kempen Léon C. , Schuuring Ed M. 
Published: March 2024

Background The detection of mutations in circulating tumor DNA (ctDNA) in blood plasma of lung cancer patients can be used to monitor the tumor-response to therapy and for the early detection of resistance mechanisms. In 2017, the Roche Cobas® EGFR Mutation Test v2 for the detection of the EGFR c.2369C&gt;T p.(T790M) mutation in plasma-derived ctDNA was FDA-approved to identify patients eligible for osimertinib treatment. Today, different platforms are available for EGFR mutation testing in plasma-derived cell-free DNA (cfDNA). In this study we compared the clinical utility of five platforms for the detection of EGFR mutations in cfDNA offering insights into their operational costs, target coverage, hands-on-time and turn-around-time.

Methods Four PCR-based platforms and one NGS-based approach for the detection of EGFR mutations were compared. Operational, maintenance, material and personnel costs were calculated for each platform and used as input variables for our recently developed ctDNA micro-costing framework (doi.org/10.1016/j.jmoldx.2022.10.004). This was compared to target coverage and turn-around-time of each platform in the context of therapy resistance.

Results Per sample costs decreased for all platforms at maximal weekly throughput. The BioCartis Idylla™ demonstrated the shortest turn-around-time while the Roche Cobas® was the least expensive. Despite being the most expensive and time-consuming, the AVENIO ctDNA Expanded kit covered the most known resistance mechanisms to EGFR inhibitors, many of which are targetable with other TKIs.

Conclusion EGFR ctDNA mutation analysis is only cost-effective when the throughput is high. This implies that centralization of cfDNA-testing is necessary to optimize cost-efficiency. With the advent of ctDNA analysis beyond EGFR in the context of targeted therapies for lung cancer, multigene detection assays will become more cost-effective with high throughput.

Overview of results Platform Turn-around time at maximal weekly throughput Per sample cost at maximal weekly throughput Coverage of resistance mutations in EGFR 1Additional testing necessary Coverage of genome-wide resistance mutations to EGFR-TKI 1Additional testing necessary BioCartis Idylla™ ctEGFR Mutation Assay 2,5 hours €571 33% 12%1 Roche Cobas® EGFR Mutation Test v2 4 hours €497 33% 6% Bio-Rad QX200 droplet digital PCR (ddPCR) 7,5 hours €766 100%1 24%1 Agena MassARRAY® UltraSEEK® Lung Panel 2 days €613 53% 12% Roche AVENIO ctDNA Expanded kit 1 week €1551 100% 65%

Citation Format: Pim Rozendal, Paul van der Leest, Elise M. van der Logt, Naomi Rifaela, Inge Platteel, Frank J. Scherpen, Harry J. Groen, Léon C. van Kempen, Ed M. Schuuring. Cost-effectiveness analysis of circulating tumor DNA-based molecular profiling platforms for the detection of EGFR mutations in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1299.