Prognostic value of neutrophil/lymphocyte ratio in intestinal and pancreatic neuroendocrine tumors: exploratory analysis of data from the CLARINET trial of lanreotide depot/autogel

Background: The CLARINET trial demonstrated longer progression free survival (PFS) among patients with inoperable/metastatic intestinal and pancreatic NETs of grade 1 or 2 (Ki67 <10%) treated with somatostatin analog lanreotide as compared to patients treated with placebo. High NLR has been reported to be prognostic of poor outcomes in majority of solid tumors. The aim of the current analysis was to evaluate the prognostic value of NLR in intestinal and pancreatic NETs.

Methods: A post-hoc exploratory analysis of CLARINET data was performed on all patients with available absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) data. Progression-free survival (PFS) curves were generated for subgroups based on NLR value using the Kaplan–Meier method and raw survival rates were computed at 24 months. P values and hazard ratios for prognostic effects were obtained using the Cox proportional hazards model.

Results: ANC and ALC were available in 201 patients: 100 patients received lanreotide and 101 patients received placebo. Baseline characteristics were balanced between the two treatment arms. The 24-month raw PFS rates across subgroups based on tertiles of the NLR distribution, irrespective of treatment, were comparable (37.3%, 38.8% and 38.8% with n=67 per group). Likewise the 24 month PFS rate was 38.1% in patients with NLR ≤4 (n=176) and 38.8% in patients with NLR >4 (n=25). These findings were corroborated by the Cox model where NLR was not found to be prognostic (p>0.6 for NLR effect irrespective of the NLR variable included). Additionally the therapeutic effect of lanreotide was independent of NLR value (p>0.1).

Conclusions: Contrary to most solid tumors, NLR seems to have no prognostic value in advanced intestinal and pancreatic NETs of grade 1–2 (Ki67 <10%). This finding, although based on relatively few patients with NLR >4 (n=25 [vs. n=176 for NLR ≤4]), might be explained by lack of inflammation affecting the tumor microenvironment in this cohort and the relatively slow rate of disease progression in the CLARINET trial.

Tal Grenader was supported by an ESMO clinical Research Fellowship Grant.

No conflict of interest.