Prevailing challenges in companion diagnostic test development for lung cancer.

[INTRODUCTION] Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and remains the leading cause of cancer-related mortality worldwide. Accurate assessment of predictive biomarkers, such as ALK and PD-L1, is essential for personalized therapy and to guide clinical decisions. Companion diagnostic (CDx) tests play a crucial role in this context.

[AREAS COVERED] PD-L1 and ALK are key predictive biomarkers for NSCLC treatment. PD-L1 expression on tumor cells (TCs) helps predict responses to anti - PD-1 and anti - PD-L1 treatments, with assays like 22C3 and SP263. ALK rearrangements, detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), helps predict responses to ALK inhibitors like crizotinib. IHC is a practical and cost-effective screening method but combining IHC with molecular techniques such as next-generation sequencing (NGS) or FISH enhances accuracy.

[EXPERT OPINION] PD-L1 and ALK are crucial predictive biomarkers for patients with NSCLC. PD-L1 IHC expression predicts response to immune checkpoint inhibitors (ICIs), but its predictive value is not perfect, with some PD-L1-negative patients benefiting from specific therapy. ALK IHC, with confirmatory FISH or NGS, guides tailored treatment. In this context, an integrated predictive approach enables the best clinical and therapeutic management of patients with NSCLC.