1. Desensitizing Effect of Cancer Cachexia on Immune Checkpoint Inhibitors in Patients With Advanced NSCLC
- Author
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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, and Toshiaki Takahashi, MD, PhD
- Subjects
Non–small cell lung cancer ,Cancer cachexia ,Programmed death 1 inhibitors ,Programmed death-ligand 1 inhibitors ,PD-L1 tumor proportion score ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
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.
- Published
- 2020
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