WCLC 2025 - Posters & ePosters-P1.11.40 The Hidden Impact of Creatinine Clearance Estimation Method on Pemetrexed-Based Chemoimmunotherapy in NSCLC With Low PD-L1 Expression

P1.11.40 The Hidden Impact of Creatinine Clearance Estimation Method on Pemetrexed-Based Chemoimmunotherapy in NSCLC With Low PD-L1 Expression

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This multicenter retrospective cohort study investigated how different creatinine clearance (Ccr) estimation methods affect the safety and efficacy of pemetrexed (PEM)-based chemoimmunotherapy in advanced non-squamous non-small cell lung cancer (NSCLC) patients with low PD-L1 expression (1-49%). Traditionally, the Jaffe method—a colorimetric assay influenced by chromogens—was used to estimate Ccr, with a safety cutoff of 45 mL/min for PEM administration. Currently, the enzymatic method, which is enzyme-based with higher specificity, is increasingly used; it tends to report lower creatinine values and thus overestimates Ccr, potentially allowing more patients to receive PEM but also increasing the risk of renal toxicity and carboplatin overdosing.<br /><br />The study included 352 eligible patients treated from 2018 to 2023. Renal function was assessed by both Jaffe and enzymatic methods, classifying patients into three cohorts: normal renal function (Ccr ≥50 mL/min by both methods), mild renal impairment (Ccr <50 enzymatic but ≥50 Jaffe), and severe renal impairment (Ccr <50 by both methods). Propensity score matching adjusted for baseline differences.<br /><br />Results showed that PEM-based chemoimmunotherapy tended to improve progression-free survival compared to non-PEM regimens in patients with normal renal function (Cohort A), with a non-significant trend in mild impairment (Cohort B), and no benefit in severe impairment (Cohort C). Overestimation of renal function by the enzymatic method reduced the observed benefit of PEM. The safety profiles (adverse events) were comparable across groups.<br /><br />The study concludes that relying solely on enzymatic Ccr can lead to inappropriate patient selection and diminish the therapeutic benefit of PEM. Using Jaffe-based or corrected renal function assessments may better identify patients who will benefit from PEM therapy while minimizing renal risks. Clinically accurate renal function evaluation is essential to optimize treatment outcomes in NSCLC with low PD-L1 expression undergoing PEM-based chemoimmunotherapy.

Asset Subtitle

Naoya Nishioka

Meta Tag

Speaker Naoya Nishioka

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

creatinine clearance

pemetrexed

chemoimmunotherapy

non-small cell lung cancer

PD-L1 expression

Jaffe method

enzymatic method

renal function assessment

progression-free survival

renal toxicity