Lactate dehydrogenase (LDH) may be a useful prognostic biomarker for patients with advanced non–small cell lung cancer (NSCLC) but it has failed to live up to hopes that it could be used to predict responses to immune checkpoint inhibitors (ICIs), Australian researchers say.
With current biomarkers such as PD-L1 expression in tumours having only limited ability to guide selection for ICI therapy, clinicians at St Georges Hospital, Sydney and the University of Sydney have been looking to other potential biomarkers such as LDH to risk-stratify patients and guide treatment selection.
As a marker of systemic inflammation and tumour burden, they noted that LDH had been found in previous retrospective studies to be associated with outcomes in patients treated with ICIs.
But data from randomised controlled trials of patients with previously treated advanced NSCLC, has provided no evidence that pretreatment LDH predicts ICI benefit, according to Dr Angelina Tjokrowidjaja and colleagues.
In the Journal Cancer they report on data from 1327 patients enrolled in the POPLAR and OAK trials of atezolizumab versus docetaxel, which showed that pretreatment LDH, whether normal or elevated, did not identify a differential benefit in favour of either atezolizumab or chemotherapy for overall survival (OS).
Similarly for progression free survival (PFS), the pretreament levels of LDH did not predict the additional benefit of either atezolizumab or chemotherapy
LDH was a prognostic marker but not a predictive marker for treatment, the researchers noted.
Elevated pretreatment LDH was associated with a higher risk of progression (hazard ratio [HR], 1.33, P < .0001) and death (HR, 1.40; P < .0001) compared to LDH within the normal range.
Likewise, persistently elevated on-treatment LDH was associated with a 1.3- to 2.8-fold increased risk of death at to six months, regardless of treatment.
An elevated pretreatment LDH level was significantly associated with worse outcomes among patients with low or undetectable PD-L1 expression (TC0/IC0) regardless of treatment. A similar non significant trend was seen in those with positive PD-L1 expression (TC1/2/3 or IC1/2/3) treated with atezolizumab, which may have reflected the small patient numbers, the researchers said.
“Our findings support the robustness of LDH as a prognostic marker, both before and on treatment, that can inform patient and clinician discussions on [NSCLC] prognosis beyond the baseline,” they wrote.
“However, our findings fail to support the use of LDH as a predictive biomarker for ICI therapy,” they added.