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Changes in the neutrophil-to-lymphocyte ratio during nivolumab monotherapy are associated with gastric cancer survival

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Abstract

Purpose

In the ATTRACTION-2 trial, nivolumab significantly improved the survival of advanced gastric cancer patients. The pretreatment neutrophil-to-lymphocyte ratio (NLR) is prognostic in patients receiving immune checkpoint inhibitors (ICIs) to treat various cancers. However, a few reports have explored the relationships between NLR changes during ICI treatment and patient survival. Here, we evaluated factors (including NLR changes in patients on nivolumab monotherapy) prognostic for gastric cancer patients.

Methods

We retrospectively analyzed 98 gastric cancer patients who received nivolumab (3 mg/kg or 240 mg/body bi-weekly) at our institution between December 2014 and September 2018. We evaluated pretreatment data, and those obtained 30 and 60 days after treatment commenced. We explored the prognostic utility of relative NLR changes in terms of the overall survival (OS) of patients on nivolumab monotherapy.

Results

Over a median of 4.9 months of follow-up, 98 gastric cancer patients received a median of four treatment courses. The overall response and disease-control rates were 25% and 52%, respectively. The median OS was 6.4 months (95% confidence interval [CI] 4.6–9.1). On multivariate analysis, factors poorly prognostic in terms of OS were an ECOG performance status of 0–1, a pretreatment NLR > 3, and an NLR difference ≧ 2 over the 60 days before and after nivolumab administration (∆NLR60). Patients with ∆NLR60 values < 2 survived significantly longer than did those with ∆NLR60 values ≧ 2 (median OS 9.2 months [95% CI 6.4–11.6] vs. 4.0 months [2.1–4.9]; P = 0.0002).

Conclusions

Nivolumab monotherapy was efficacious in gastric cancer patients. NLR changes during such therapy may be predictive of outcomes.

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Abbreviations

ICI:

Immune checkpoint inhibitor

NLR:

Neutrophil-to-lymphocyte ratio

irAE:

Immune-related adverse event

CI:

Confidence interval

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Acknowledgements

We thank all participating patients, and our colleagues who advised us on study design, data analysis, and manuscript preparation.

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Authors and Affiliations

  1. Department of Gastrointestinal Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Yumiko Ota, Daisuke Takahari, Takeshi Suzuki, Hiroki Osumi, Izuma Nakayama, Akira Oki, Takeru Wakatsuki, Takashi Ichimura, Mariko Ogura, Eiji Shinozaki, Mitsukuni Suenaga, Keisho Chin & Kensei Yamaguchi

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  1. Yumiko Ota
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  2. Daisuke Takahari
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Correspondence to Daisuke Takahari.

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Ota, Y., Takahari, D., Suzuki, T. et al. Changes in the neutrophil-to-lymphocyte ratio during nivolumab monotherapy are associated with gastric cancer survival. Cancer Chemother Pharmacol 85, 265–272 (2020). https://doi.org/10.1007/s00280-019-04023-w

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