• Stefanie Schatz, Markus Falk, Balázs Jóri, Hayat O Ramdani, Stefanie Schmidt, Eva-Maria Willing, Roopika Menon, Groen Harry J M HJM Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands., Linda Diehl, Matthias Kröger, Claas Wesseler, Frank Griesinger, Petra Hoffknecht, Markus Tiemann, and Lukas C Heukamp.
• Institut für Hämatopathologie Hamburg, Fangdieckstraße 75A, 22547 Hamburg, Germany.
• Cancers (Basel). 2020 Jun 24; 12 (6).

AbstractIn recent years, Non-small cell lung cancer (NSCLC) has evolved into a prime example for precision oncology with multiple FDA-approved "precision" drugs. For the majority of NSCLC lacking targetable genetic alterations, immune checkpoint inhibition (ICI) has become standard of care in first-line treatment or beyond. PD-L1 tumor expression represents the only approved predictive biomarker for PD-L1/PD-1 checkpoint inhibition by therapeutic antibodies. Since PD-L1-negative or low-expressing tumors may also respond to ICI, additional factors are likely to contribute in addition to PD-L1 expression. Tumor mutation burden (TMB) has emerged as a potential candidate; however, it is the most complex biomarker so far and might represent a challenge for routine diagnostics. We therefore established a hybrid capture (HC) next-generation sequencing (NGS) assay that covers all oncogenic driver alterations as well as TMB and validated TMB values by correlation with the assay (F1CDx) used for the CheckMate 227 study. Results of the first consecutive 417 patients analyzed in a routine clinical setting are presented. Data show that fast reliable comprehensive diagnostics including TMB and targetable alterations are obtained with a short turn-around time. Thus, even complex biomarkers can easily be implemented in routine practice to optimize treatment decisions for advanced NSCLC.

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