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The efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer with liver metastases

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Abstract

Objectives

Although liver metastasis has been known to be associated with poor prognosis, only a few studies have shown an association between liver metastasis and treatment outcomes with immune checkpoint inhibitors (ICI). Furthermore, factors associated with prognosis have remained unclear. The present study therefore evaluates the efficacy of nivolumab, pembrolizumab, and atezolizumab among patients with non-small cell lung cancer (NSCLC) who had liver metastasis and identifies factors correlated with prognosis.

Materials and methods

A total of 215 patients with advanced and recurrent NSCLC who received ICI therapy at a single center were retrospectively reviewed. A total of 41 patients (19.1%) had liver metastasis upon initiation of ICI therapy. Overall, 125, 64, and 26 patients were treated with nivolumab, pembrolizumab, and atezolizumab, respectively.

Results

Among the included patients, those with liver metastasis had shorter overall survival (OS) [hazard ratio (HR), 2.04; 95% CI 1.33–3.13] and progression-free survival (PFS) (HR, 1.89; 95% CI 1.29–1.71) compared to those without the same. Patients with liver metastasis had a response rate (RR) of 22.5%. Among patients with liver metastasis, inferior OS was associated with low albumin, poor Eastern Cooperative Oncology Group performance status, driver mutation, and number of liver metastasis (≥ 5). Moreover, patients with liver metastasis who had good Royal Marsden Hospital (0–1) and Gustave Roussy Immune (0–1) scores showed significantly longer OS and PFS.

Conclusion

Despite the poor outcomes with ICI treatment in patients with advanced and recurrent NSCLC who had liver metastasis, some characteristics among patients with liver metastasis may be associated with prognosis.

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Abbreviations

ICI:

Immune checkpoint inhibitors

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PFS:

Progression-free survival

ECOG PS:

Eastern Cooperative Oncology Group performance status

PD-1:

Programmed cell death protein-1

PD-L1:

Programmed cell death-ligand-1

RR:

Response rate

DCR:

Disease control rate

LDH:

Lactate dehydrogenase

NLR:

Neutrophil-to-lymphocyte ratio

RECIST:

Response evaluation criteria in solid tumors

GRIm Score:

Gustave Roussy immune score

RMH Score:

Royal Marsden Hospital Score

References

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Acknowledgments

We thank Enago (https://www.enago.jp/) for the English language review.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

Authors

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Correspondence to Yusuke Okuma.

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Conflict of interest

YO has received honoraria from AstraZeneca Japan, Boehringer-Ingelheim Japan, Chugai Pharmaceutical Co. Ltd., Eli Lily Co. Ltd., MSD K. K., and Ono Pharmaceutical Co. The other authors have no conflicts of interest to disclose.

Ethical approval

This study protocol was approved by the Ethics Committee of the Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (#2272) and was conducted in accordance with the tenets of the Declaration of Helsinki.

Informed consent

Instead of obtaining informed consent from each patient, participants or their next of kin were given the opportunity to opt-out.

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Kitadai, R., Okuma, Y., Hakozaki, T. et al. The efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer with liver metastases. J Cancer Res Clin Oncol 146, 777–785 (2020). https://doi.org/10.1007/s00432-019-03104-w

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  • DOI: https://doi.org/10.1007/s00432-019-03104-w

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