JTO Clinical and Research Reports (Jun 2020)

Desensitizing Effect of Cancer Cachexia on Immune Checkpoint Inhibitors in Patients With Advanced NSCLC

  • Taichi Miyawaki, MD,
  • Tateaki Naito, MD, PhD,
  • Akihro Kodama, MD,
  • Naoya Nishioka, MD,
  • Eriko Miyawaki, MD,
  • Nobuaki Mamesaya, MD,
  • Takahisa Kawamura, MD, PhD,
  • Haruki Kobayashi, MD,
  • Shota Omori, MD,
  • Kazushige Wakuda, MD,
  • Akira Ono, MD, PhD,
  • Hirotsugu Kenmotsu, MD, PhD,
  • Haruyasu Murakami, MD, PhD,
  • Akifumi Notsu, PhD,
  • Keita Mori, PhD,
  • Hideyuki Harada, MD, PhD,
  • Masahiro Endo, MD, PhD,
  • Kazuhisa Takahashi, MD, PhD,
  • Toshiaki Takahashi, MD, PhD

Journal volume & issue
Vol. 1, no. 2
p. 100020

Abstract

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Introduction: Programmed cell death 1 (PD-1) inhibitors have become standard treatment for patients with advanced NSCLC. However, few studies have focused on the impact of cancer cachexia on the efficacy of PD-1 or programmed death-ligand 1 (PD-L1) inhibitors among patients with NSCLC. Methods: We retrospectively reviewed medical records of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy from May 2016 to December 2018. We defined cancer cachexia as unintentional weight loss greater than 5% over 6 months and high PD-L1 as greater than 50% expression on tumor cells. We evaluated the objective response rates (ORRs) and progression-free survival (PFS). Results: Among 108 patients, 52 had cancer cachexia. Patients with cachexia had a lower ORR (15% versus 57%, p < 0.001) and shorter PFS (2.3 mo versus 12.0 mo, p < 0.001) than those without cachexia. Patients with low PD-L1 expression had a lower ORR (14% versus 53%, p < 0.001) and shorter PFS (2.8 mo versus 10.8 mo, p = 0.002) than those with high PD-L1 expression. Multivariate analysis revealed cancer cachexia and low PD-L1 expression as independent negative predictors of PFS. Among patients with cachexia, there was no significant difference in the ORR (p = 0.514) or PFS (p = 0.992) on the basis of PD-L1 expression. Conclusions: Our findings indicate that cancer cachexia might be a negative predictor of the efficacy of PD-1 or PD-L1 inhibitors and reduce the impact of PD-L1 expression on the effect of PD-1 or PD-L1 inhibitors in patients with advanced NSCLC. Further clinical and basic studies are needed.

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