P3.02c-063 Lactate Dehydrogenase (LDH) as a Surrogate Biomarker to Checkpoint-Inhibitors for Patient with Advanced Non–Small-Cell Lung Cancer (NSCLC)

Castro, Am Martinez De; Navarro, Alejandro; Pérez, Susana Cedrés; Martinez, A.; Pardo, Núria; Hernando, Alberto; Ortiz, Carolina; Amair, F.; Biosca, M.; Aguilar-Company, Juan; Scheenaard, Eulalia; Recasens, Sergi; Carbonell, Luis F.; Retter, Andrea; Martínez, S. Torres; Piera, Adelaida; Valverde, Silvia; Velez, L.; Matas, Silvia García; Vilaró, Marta; Felip, Enriqueta

doi:10.1016/j.jtho.2016.11.1858

Cited by 7 publications

(13 citation statements)

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“…The clinical utility of LDH lies in its prognostic ability. Our findings are consistent with earlier studies of pretreatment LDH as a prognostic marker in patients with advanced NSCLC treated with ICIs 13,14,22‐24 . In a meta‐analysis of retrospective studies of patients with NSCLC treated with ICIs, high pretreatment LDH was significantly associated with poor PFS and OS 14 .…”

Section: Discussionsupporting

confidence: 91%

“…However, further research is required, as we do not advocate using on‐treatment LDH as a sole determinant for decisions around treatment cessation. Others have reported the potential value of combining the baseline and the relative change in LDH on treatment with C‐reactive protein, the neutrophil to lymphocyte ratio, and the tumor size to develop a risk score to predict radiological disease progression 24 . In particular, future studies could focus on validating pre‐ and on‐treatment LDH combined with other inflammatory and/or novel biomarkers such as circulating tumor DNA 26,27 as part of a risk tool using high‐quality and large data sets.…”

Section: Discussionmentioning

confidence: 99%

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Pre‐ and on‐treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non–small cell lung cancer

Tjokrowidjaja

Lord

John

et al. 2022

Cancer

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BACKGROUND:The survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are variable. This study investigated whether pre-and on-treatment lactate dehydrogenase (LDH) could better prognosticate and select patients for ICI therapy. METHODS: Using data from the POPLAR and OAK trials of atezolizumab versus docetaxel in previously treated advanced NSCLC, the authors assessed the prognostic and predictive value of pretreatment LDH (less than or equal to vs greater than the upper limit of normal). They further examined changes in on-treatment LDH by performing landmark analyses and estimated overall survival (OS) distributions according to the LDH level stratified by the response category (complete response [CR]/ partial response [PR] vs stable disease [SD]). They repeated pretreatment analyses in subgroups defined by the programmed death ligand 1 (PD-L1) status. RESULTS: This study included 1327 patients with available pretreatment LDH. Elevated pretreatment LDH was associated with an adverse prognosis regardless of treatment (hazard ratio [HR] for atezolizumab OS, 1.49; P = .0001; HR for docetaxel OS, 1.30; P = .004; P for treatment by LDH interaction = .28). Findings for elevated pretreatment LDH were similar for patients with positive PD-L1 expression treated with atezolizumab. Persistently elevated on-treatment LDH was associated with a 1.3-to 2.8-fold increased risk of death at weeks 6, 12, 18, and 24 regardless of treatment. Elevated LDH at 6 weeks was associated with significantly shorter OS regardless of radiological response (HR for CR/PR, 2.10; P = .04; HR for SD, 1.50; P < .01), with similar findings observed at 12 weeks. CONCLUSIONS: In previously treated advanced NSCLC, elevated pretreatment LDH is an independent adverse prognostic marker. There is no evidence that pretreatment LDH predicts ICI benefit. Persistently elevated on-treatment LDH is associated with worse OS despite radiologic response.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Pre‐ and on‐treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non–small cell lung cancer

Tjokrowidjaja

Lord

John

et al. 2022

Cancer

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“…LDH has been found associated with poor prognosis when increased from 1 to 2.5 times ULN in patients treated with chemotherapy or targeted therapies . However, the effect of inflammatory status on benefit of ICI treatment in NSCLC patients is not well known yet, although some retrospective studies have shown that those with a high pretreatment of LDH level had a significantly shorter survival than those with normal LDH level …”

Section: Discussionmentioning

confidence: 99%

Pretreatment lactate dehydrogenase may predict outcome of advanced non small‐cell lung cancer patients treated with immune checkpoint inhibitors: A meta‐analysis

et al. 2019

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The main aim of this study is to investigate whether baseline lactate dehydrogenase (LDH) is associated with the clinical outcome of non small‐cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). We searched Pubmed, the Cochrane Central library and Embase for peripheral blood biomarker of LDH in advanced NSCLC patients treated with ICIs. We extracted the hazard ratio (HR) with 95% confidence interval (CI) for the progression free survival (PFS) and overall survival (OS) and performed meta‐analysis of HR. Pooled estimates of treatment outcomes were calculated by stata 15.1. Six studies with 1136 patients were included in this study. The pooled results of univariate analysis suggested that an elevated pretreatment LDH level was correlated with significant shorter PFS (HR = 1.53, 95% CI 1.27‐1.83, P < 0.001) and OS (HR = 2.11, 95% CI 1.43‐3.11, P < 0.001). The association remained significant in the multivariate analysis that elevated pretreatment LDH level was associated with poor PFS (HR = 1.62, 95% CI 1.26‐2.08, P < 0.001) and OS (HR = 2.38, 95% CI 1.37‐4.12, P = 0.002). A high pretreatment LDH level was significantly correlated with shorter PFS and OS. Pretreatment LDH may serve as a predictive biomarker for advanced NSCLC patients treated with ICIs.

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“…Finally, several exploratory studies provided a clue that baseline level of serum LDH may contribute to the identification of patients with NSCLC gaining better survival benefits from immunotherapy. Researchers evaluated the LDH level in 94 NSCLC patients treated with ICIs, and discovered that baseline LDH < 400 was related to improved OS (HR = 0.45, p = 0.01) (32). Further studies involving large-scale prospective cohorts may facilitate the progress in confirming the function of elevated LDH in NSCLC and its potential value in predicting efficacy.…”

Section: Routine Peripheral Blood Biomarkersmentioning

confidence: 99%

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

Zhang

Pang

et al. 2020

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) have brought impressive clinical benefits in a variety of malignancies over the past years, which dramatically revolutionized the cancer treatment paradigm. Monotherapy or in combination with chemotherapy of ICIs targeting programmed death 1/programmed death ligand 1 (PD-L1) has emerged as an alternative treatment for patients with advanced non-small-cell lung cancer (NSCLC). However, constrained by primary or acquired resistance, most patients obtain limited benefits from ICIs and occasionally suffer from severe immune-related adverse events. Moreover, owing to the complexity of the tumor microenvironment and the technical limitations, clinical application of PD-L1 and tumor mutation burden as biomarkers shows many deficiencies. Thus, additional predictive biomarkers are required to further advance the precision of proper patient selection, avoiding the exposure of potential nonresponders to unnecessary immunotoxicity. Nowadays, an increasing number of investigations are focusing on peripheral blood as a noninvasive alternative to tissue biopsy in predicting and monitoring treatment outcomes. Herein, we summarize the emerging blood-based biomarkers that could predict the clinical response to checkpoint immunotherapy, specifically in patients with NSCLC.

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P3.02c-063 Lactate Dehydrogenase (LDH) as a Surrogate Biomarker to Checkpoint-Inhibitors for Patient with Advanced Non–Small-Cell Lung Cancer (NSCLC)

Cited by 7 publications

References 0 publications

Pre‐ and on‐treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non–small cell lung cancer

Pre‐ and on‐treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non–small cell lung cancer

Pretreatment lactate dehydrogenase may predict outcome of advanced non small‐cell lung cancer patients treated with immune checkpoint inhibitors: A meta‐analysis

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer

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