Integration of Tumor Mutation Burden and PD-L1 Testing in Routine Laboratory Diagnostics in Non-Small Cell Lung...

Area of Science:

• Oncology
• Genomics
• Cancer Diagnostics

Background:

• Non-small cell lung cancer (NSCLC) treatment increasingly relies on precision oncology and immune checkpoint inhibition (ICI).
• PD-L1 expression is the sole approved biomarker for ICI, but its limitations necessitate additional predictive factors.
• Tumor mutation burden (TMB) shows promise as a biomarker but presents diagnostic challenges.

Purpose of the Study:

• To establish and validate a hybrid capture (HC) next-generation sequencing (NGS) assay for comprehensive NSCLC diagnostics.
• To assess the feasibility of implementing complex biomarkers like TMB in routine clinical practice.
• To evaluate the turnaround time and reliability of the developed assay.

Main Methods:

• Development of a hybrid capture (HC) next-generation sequencing (NGS) assay covering oncogenic driver alterations and TMB.
• Validation of TMB values against the F1CDx assay used in the CheckMate 227 study.
• Analysis of data from the first 417 consecutive NSCLC patients in a routine clinical setting.

Main Results:

• The HC-NGS assay successfully provided fast, reliable, and comprehensive diagnostic results.
• The assay accurately determined both targetable genetic alterations and TMB.
• Short turnaround times were achieved, facilitating routine clinical implementation.

Conclusions:

• Comprehensive diagnostics, including TMB and driver alterations, can be efficiently implemented in routine practice for advanced NSCLC.
• This approach optimizes treatment decisions for NSCLC patients, particularly those lacking targetable mutations.
• The developed HC-NGS assay addresses the need for robust and accessible biomarker analysis in precision oncology.