Abstract
Background: Recent studies have revealed that liver metastasis is associated with poor outcomes after treatment using immune checkpoint inhibitors, although the cause remains unclear. Patients and Methods: We retrospectively identified 201 patients at three Japanese Centers who received nivolumab for advanced non-small cell lung cancer between December 2015 and July 2016. The patients' baseline clinical characteristics and subsequent outcomes were compared according to liver metastasis status. Results: Liver metastasis was associated with inferior progression-free survival (PFS) and a lower response rate. Additionally, liver metastasis was significantly associated with younger age, poorer Eastern Cooperative Oncology Group performance status (ECOG PS), and more metastatic sites. Multivariate analyses revealed that poor PFS was independently associated with poor baseline ECOG PS (p=0.039) and high number of metastatic sites (p=0.007), although liver metastasis (p=0.2) was not. Conclusion: Baseline clinical characteristics were a strong predictor of outcome in nivolumab-treated patients with liver metastasis.
- Nivolumab
- immune checkpoint inhibitor
- liver metastasis
- non-small cell lung cancer
- neutrophil–to–lymphocyte ratio
- NLR
Footnotes
Conflicts of interest
T. Shiroyama received grants and lecture fees from Ono Pharmaceutical and grants from Bristol-Myers Squibb during the study, as well as lecture fees from Taiho Pharmaceutical, Boehringer Ingelheim, and AstraZeneca that were unrelated to the submitted work. H. Suzuki received grants and lecture fees from Ono Pharmaceutical and grants from Bristol-Myers Squibb during the study, as well as lecture fees from Taiho Pharmaceutical, Boehringer Ingelheim, Pfizer, and Eli-Lilly that were unrelated to the submitted work. M. Tamiya received grants and lecture fees from Ono Pharmaceutical and grants from Bristol-Myers Squibb during the study, as well as lecture fees from Chugai Pharmaceutical, Pfizer, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Asahi Kasei Pharmaceutical, Daichi Sankyo CO. LTD., and Alere Medical that were unrelated to the submitted work. A. Tamiya received grants and lecture fees from Ono Pharmaceutical and Bristol-Myers Squibb during the study, as well as lecture fees from Chugai Pharmaceutical, AstraZeneca, Eli Lilly, and Boehringer Ingelheim that were unrelated to the submitted work. A. Tanaka received grants and lecture fees from Ono Pharmaceutical and grants from Bristol-Myers Squibb during the study, as well as lecture fees from Siemens and Chugai Pharmaceutical that were unrelated to the submitted work. N. Okamoto received grants from Ono Pharmaceutical and Bristol-Myers Squibb during the study, as well as lecture fees from AstraZeneca that were unrelated to the submitted work. K. Nakahama received grants from Ono Pharmaceutical and Bristol-Myers Squibb during the study. Y. Taniguchi received grants from Ono Pharmaceutical and Bristol-Myers Squibb during the study, as well as lecture fees from Chugai Pharmaceutical that were unrelated to the submitted work. S. Isa received grants from Ono Pharmaceutical and Bristol-Myers Squibb during the study. T. Inoue received grants and lecture fees from Ono Pharmaceutical and grants from Bristol-Myers Squibb during the study, as well as lecture fees from Boehringer Ingelheim that were unrelated to the submitted work. F. Imamura received grants and lecture fees from Ono Pharmaceutical and Bristol-Myers Squibb during the study, as well as lecture fees from Pfizer Inc., AstraZeneca K. K., Novartis Pharma K. K. Kyowa Hakko Kirin Co. Ltd., Boehringer Ingelheim, Taiho Pharmaceutical Co. Ltd., Eli Lilly Japan K. K., and Chugai Pharmaceutical Co. Ltd. that were unrelated to the submitted work. S. Atagi received grants and lecture fees from Ono Pharmaceutical and Bristol-Myers Squibb during the study, as well as grants from Pfizer, Chugai Pharmaceutical, AstraZeneca, Taiho Pharmaceutical, Yakult Pharmaceutical Industry, MSD, Eli Lilly, and Boehringer Ingelheim, in addition to lecture fees from Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Eli Lilly, and Boehringer Ingelheim that were unrelated to the submitted work. T. Hirashima received grants and lecture fees from Ono Pharmaceutical and Bristol-Myers Squibb during the study, as well as grants and lecture fees from MSD Oncology, AstraZeneca, Eli Lilly Japan, Chugai Pharma, and Boehringer Ingelheim, in addition to grants from Eisai, Daiichi Sankyo, Merck Serono, Taiho Pharmaceutical, Kyowa Hakko Kirin, and Takeda, plus lecture fees from Bayer, that were unrelated to the submitted work.
Ethical approval
All study procedures complied with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments.
Informed Consent
All patients provided written informed consent for the treatment using nivolumab.
Funding
This study was supported by Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb, although these sponsors played no role in the study design, data collection and analysis, decision to publish, or preparation of the article.
- Received June 14, 2018.
- Revision received June 25, 2018.
- Accepted June 28, 2018.
- Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved