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

Angelina Tjokrowidjaja; Sarah J Lord; Thomas John; Craig R Lewis; Peey-Sei Kok; Ian C Marschner; Chee K Lee

doi:10.1002/cncr.34113

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

Cancer. 2022 Apr 15;128(8):1574-1583. doi: 10.1002/cncr.34113. Epub 2022 Jan 28.

Authors

Angelina Tjokrowidjaja^{1

2}, Sarah J Lord^{1

3}, Thomas John⁴, Craig R Lewis⁵, Peey-Sei Kok¹, Ian C Marschner¹, Chee K Lee^{1

2}

Affiliations

¹ National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.
² Department of Medical Oncology, St George Hospital, Kogarah, New South Wales, Australia.
³ School of Medicine, University of Notre Dame, Sydney, New South Wales, Australia.
⁴ Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
⁵ Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia.

Abstract

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.

Keywords: advanced lung cancer; biomarker; lactate dehydrogenase (LDH); predictive; prognosis.

MeSH terms

Biomarkers
Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
L-Lactate Dehydrogenase
Lung Neoplasms* / drug therapy
Prognosis

Substances

Biomarkers
L-Lactate Dehydrogenase