PD-L1 Immunohistochemistry-Discrepant Results Between Synchronous Tumor Samples May Cause More Treatment Choice Dilemmas Than Molecular Heterogeneity in Patients With Advanced Non-Small Cell Lung Cancers.

Abstract

Biomarker analyses have become mandatory for treatment choices in patients with advanced non-small cell lung cancers. PD-L1 expression for immunotherapy as well as oncogenic molecular alterations for targeted therapies must be analyzed in tumor samples. Intersample heterogeneity may cause dilemmas in treatment choices when faced with discrepant biomarker results. We led a retrospective study evaluating the potential impact on guideline-based therapeutic decisions of biomarker analyses performed in several synchronous tumor samples per patient. We collected retrospective data about patients with advanced non-small cell lung cancers, and synchronous tumor paired samples were analyzed for PD-L1 immunohistochemistry (IHC) and oncogene molecular statuses. Among 34 patients, none had a discrepant result between paired samples with respect to oncogene molecular statuses. At the opposite, intersample-discrepant PD-L1 IHC results may have caused treatment choice dilemmas for 6 (17.6%) patients discussing first-line therapy options (ie, immune checkpoint inhibitor therapy versus other systemic therapy with regard to the threshold of ≥50% PD-L1 IHC-positive tumor cells). In addition, for 6 (17.6%) other patients, different PD-L1 IHC results may have also influenced the choice of one therapy or another in second-line therapy (ie, with regard to the threshold of ≥1% PD-L1 IHC-positive tumor cells). In our case series, discrepant results with regard to PD-L1 IHC between paired tumor samples could generate more treatment choice dilemmas than the molecular heterogeneity of oncogenic drivers.