Assessing the predictive role of platelet-lymphocyte ratio in EGFR-mutated non-small cell lung cancer patients treated with tyrosine kinase inhibitors: an analysis across TKI generations.

Introduction: The predictive utility of laboratory markers in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) is an ongoing area of research. The predictability of the platelet-lymphocyte ratio (PLR) on survival outcomes depending on the generation of EGFR TKI is undetermined.
Methods: 151 patients treated with EGFR TKIs in Los Angeles were grouped according to generation of TKI. Differences in progression free survival (PFS) by stratification by PLR was determined using Kaplan-Meier analysis. Differences in median change in laboratory markers by generation of TKI was analyzed using Mann-Whitney tests. Cox Hazard Regression was used to perform multivariate analysis.
Results: Median PFS of those managed with 1st or 2nd generation TKIs was significantly lower in patients with a PLR ≥ 180 (10.5 months) compared to those with PLR < 180 (16.6 months, p = 0.0163). Median PFS was comparable in those treated with osimertinib regardless of PLR. Patients managed with osimertinib had a significant decrease in absolute lymphocyte count (ALC) at 6 weeks and in platelets at 6 weeks and 3 months compared to those managed with 1st or 2nd generation TKIs.
Discussion: The predictive value of PLR was more apparent in patients treated with 1st or 2nd generation TKIs compared to those treated with osimertinib. Third generation EGFR TKIs may be more efficacious in treating patients with laboratory findings previously shown to predict poor survival. The significant changes in peripheral cell counts suggest variable tumor microenvironment changes dependent on the generation of TKI received.
Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the ethical standards as defined by the 1964 Declaration of Helsinki and its later amendments. Ethics approval for use of our lung cancer database was granted by the University of Southern California’s Institutional Review Board (IRB): HS-15-00200 Retrospective Analysis of Lung Cancer Patients Treated at LAC-USC Medical Center and USC Norris Comprehensive Cancer Center. IRB approval was initially submitted on 3/26/2015 and has been approved annually with the last approval date of 6/13/2024 and expiration date of 6/12/2025. The need for informed consent was waived as the study was retrospective in nature. Competing interests: Dr. Robert Hsu is a consultant for Targeted Oncology and Takeda and received honoraria from DAVA Oncology and The Dedham Group. Dr. Jorge Nieva is a consultant for Aadi Biosciences, Affyimmune, ANP Technologies, Astra Zeneca, BioAtla, G1 Therapeutics, Genetech, Kalivir Mindmed, Naveris, Sonofi, receives research support from Genetech and Merck, owns intellectual property with Cansera, and has ownership interests with Cansera, Indee Bio, Quantgene, Amgen, Johnson & Johnson, and Novartis. Jacob Thomas is a consultant for Coherus BioSciences, Inc. and Kura Oncology, Inc. The remaining authors have no conflicts of interest to disclose.
(© 2024. The Author(s).)