Original ResearchNeutrophil-lymphocyte ratio kinetics in patients with advanced solid tumours on phase I trials of PD-1/PD-L1 inhibitors
Section snippets
Background
The advent of new cancer immunotherapeutics has led to renewed optimism in clinically meaningful progress to improve cancer outcomes for patients. In particular, since a survival benefit was observed with ipilimumab, an immune checkpoint inhibitor (ICI), in patients with advanced melanoma [1], there has been an explosion in novel cancer immunotherapeutics. The most successful molecules to date have been inhibitors of the programmed-death 1 (PD-1) – programmed death-ligand 1 (PD-L1) checkpoint,
Study design
We conducted a retrospective multi-centre cohort study of consecutive patients with advanced solid tumours treated with PD-1/PD-L1 inhibitors in phase I clinical trials across three sites in the United Kingdom, Spain and Australia. At least one dose of experimental agent needed to be received to be eligible for inclusion on this study. Data collected included patient demographics and clinical data, haematology and biochemistry at baseline and before each cycle of therapy, toxicity data,
Results
Between May 2014 and May 2017, 165 patients were treated with PD-1 and PD-L1 inhibitors. Baseline characteristics are displayed in Table 1. Baseline characteristics were well balanced by baseline NLR status although patients with higher baseline NLR were more likely to have received previous radiotherapy treatment (p = 0.03). Patients with higher baseline NLR were observed to have lower baseline haemoglobin (p < 0.001) and lower baseline albumin (p < 0.001).
Overall, 79/165 (48%) achieved a CB.
Discussion
The NLR is a widely validated clinical biomarker of prognosis applicable to several clinical settings. Its role in the immunotherapy era is undefined, although studies have shown that for melanoma patients treated with the CTLA-4 inhibitor, ipilimumab, the NLR retains its prognostic significance [22]. This study suggests that baseline NLR is correlated with clinical benefit, and that it is significantly prognostic for OS in a population of patients with advanced solid tumours participating in
Conflict of interest statement
None declared.
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Contributed equally.