Early predictive biomarkers could identify non-responders to PD-1/PD-L1-Inhibitors

Treatment with PD-1/PD-L1 inhibitors is now the standard of care for patients with advanced non-small cell lung cancer. PD-L1 expression, in addition to interferon score and tumour mutational burden, are predictive biomarkers, however early clinical predictive biomarkers are lacking.
Kumar R et al. (abstract P2.07-049) showed that changes in lactate dehydrogenase (LDH) above the upper limit of normal values at cycle 2 and in neutrophil-lymphocyte ratio (NLR) ≥ 5 at 6 weeks predicts for disease progression at the first tumour response evaluation (TRE). These routine early predictive biomarkers could be used to identify non-responders when treating with PD-1/PD-L1 inhibitors prior to a CT scan.

The study

Patients with NSCLC who received treatment with PD-1/PD-L1 inhibitors between 1 Jan 2014 – 31 Dec 2016 were retrospectively identified from electronic health records.
91 patients were identified, with a mean age of 65 years, of whom 52 % were male. The majority were ex-smokers (69.2 %), followed by never smokers (23.1 %). Non-squamous histology was seen in 59.3 % of patients and 86.8 % of the patients had ECOG performance status 0-1.
The LDH at baseline, cycle 2, and a change-in LDH ≥ 10 % at cycle 2 and 6 weeks was no predictive factor for the disease control rate (DCR) at the first TRE. A LDH ≥ upper limit of normal at 6 weeks did predict disease progression at the first TRE (p = 0.04), with an OR of 3.58 (95 % CI 1.11–11.52).
The NLR at baseline and 6 weeks, and the change-in NLR > 10 % at cycle 2 and 6 weeks was no predictive factor for the DCR at the first TRE. A NLR ≥ 5 at cycle 2 did predict a disease progression at the first TRE (p = 0.008), with an OR of 3.92 (95 % CI 1.48–10.39).
Receiver operator curve analysis of the early LDH/NLR score (1 point each for 6 week LDH ≥ upper limit of normal and cycle 2 NLR ≥5) was a predictive factor for disease progression at the first TRE (C-index 0.77, P-value <0.0001).