WCLC 2025 - Posters & ePosters-P2.06.72 Impact of Peripheral Electrolyte on Equilibrium Between Immunotherapy Toxicity and Survival in Advanced NSCLC Treated With PD-L1 Blockade

P2.06.72 Impact of Peripheral Electrolyte on Equilibrium Between Immunotherapy Toxicity and Survival in Advanced NSCLC Treated With PD-L1 Blockade

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This study by Ning Gao et al. explores the role of baseline peripheral electrolyte levels as predictive biomarkers for immune-related adverse events (irAEs) and survival in advanced non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 immune checkpoint inhibitors (atezolizumab). Immune toxicity often limits immunotherapy benefits, yet biomarkers predicting toxicity remain scarce. Since electrolyte homeostasis influences immune function, the study hypothesized that baseline serum electrolytes might predict irAE risks and distinguish toxicity signals from treatment efficacy.<br /><br />The authors analyzed clinical data and baseline serum electrolyte concentrations from two phase III randomized trials (1OAK and 2POPLAR) comparing atezolizumab to docetaxel in advanced NSCLC. Associations between six baseline electrolytes and irAEs, progression-free survival, and overall survival were assessed via multivariable Cox and logistic regression models. Analyses targeted overall, organ-specific, and severe (grade 3) irAEs. A parallel evaluation in the docetaxel arm helped confirm immunotherapy-specific effects.<br /><br />The key findings showed that elevated baseline serum calcium predicted increased risk of any-grade and severe irAEs, particularly endocrine toxicities, but did not correlate with survival outcomes, indicating its specific role as a toxicity biomarker. Conversely, higher baseline chloride was linked to both higher irAE incidence (notably gastrointestinal irAEs) and improved survival, suggesting it reflects both immune toxicity and antitumor efficacy. These electrolyte-irAE associations were specific to the immunotherapy cohort, as no similar patterns emerged in docetaxel-treated patients.<br /><br />Clinically, routine measurement of baseline calcium could identify patients at higher risk for immunotherapy-related toxicities and guide closer monitoring or preventive interventions. The study supports the immunotherapy-specific relevance of electrolyte levels in predicting toxicity and balancing efficacy. Future work aims for prospective validation, dynamic electrolyte monitoring, mechanistic exploration of electrolyte-immune interactions, and development of clinical risk prediction tools embedded in electronic health records to reduce severe irAEs without compromising treatment benefits.

Asset Subtitle

Ning Gao

Meta Tag

Speaker Ning Gao

Topic Pathology and Biomarkers

Keywords

non-small cell lung cancer

NSCLC

immune-related adverse events

irAEs

immune checkpoint inhibitors

PD-1/PD-L1

atezolizumab

baseline serum electrolytes

calcium

chloride