Implementation of Real-World Diagnostic Strategies in Taiwan for the Identification of Targetable Oncogenic Driver Alterations in Non-Small Cell Lung Cancer.

Abstract

Purpose: Next-generation sequencing is optimal for testing advanced/metastatic non-small cell lung cancer (NSCLC) biomarkers; however, implementation and access are often hindered across Asia by turnaround time (TAT), logistics, and reimbursement. This study aimed to implement a multigene biomarker testing algorithm for the comprehensive detection of actionable NSCLC biomarkers.

Methods: The AmoyDx PLC Panel, a multigene polymerase chain reaction (PCR), was used in testing, with an optimal workflow developed in Chi Mei Medical Center, Taiwan. Tests were conducted on 897 NSCLC samples between June 2022 and November 2023.

Results: Among the tested samples, 83.0% were adenocarcinoma, with 74.4% at stage IV. Most samples were successfully analyzed for additional biomarkers, with 1.3% and 2.1% of samples having insufficient tissue or DNA quality, and insufficient RNA quality, respectively. This study reflected clinical reality, with most samples tested at initial diagnosis (72.0%). Other patients had previous single-gene testing for epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) with negative results (11.2%), and others were tested after progression on tyrosine kinase inhibitors (16.8%). The median testing TAT was short (4 days). Of the patients tested at diagnosis (n = 638), 50.6% had EGFR mutations and 79 (12.4%) patients had alterations in Kirsten RAat Sarcoma viral oncogene homolog (KRAS) G12C (2.4%), v-raf murine sarcoma viral oncogene homolog B1 (BRAF) (0.9%), human epidermal growth factor receptor 2 (HER2) (3.5%), mesenchymal-epithelial transition factor (MET) (2.4%), ALK (1.3%), ROS1 (1.6%), and rearranged during transfection (RET) (0.5%). Among the 99 patients who had previously tested negative for EGFR/ALK/ROS1, 47 (47.5%) patients had biomarker alterations that were potentially targetable by available drugs.

Conclusion: This study highlighted the effectiveness of multigene PCR testing in identifying actionable NSCLC biomarkers for low failure rate, short TAT, and minimal tissue requirements, enabling timely, personalized interventions. The workflow implemented at Chi Mei Medical Center provides a model that other hospitals can adopt to overcome testing barriers and improve precision oncology access.