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. 2022 Feb;71(2):387-398.
doi: 10.1007/s00262-021-02997-2. Epub 2021 Jun 27.

Prognostic significance of cachexia in advanced non-small cell lung cancer patients treated with pembrolizumab

Hitomi Jo  1   2   3 , Tatsuya Yoshida  4   5 , Hidehito Horinouchi  1 , Shigehiro Yagishita  2 , Yuji Matsumoto  1   6 , Yuki Shinno  1 , Yusuke Okuma  1 , Yasushi Goto  1 , Noboru Yamamoto  1   7 , Kazuhisa Takahashi  3 , Noriko Motoi  8 , Yuichiro Ohe  1
Affiliations

Prognostic significance of cachexia in advanced non-small cell lung cancer patients treated with pembrolizumab

Hitomi Jo et al. Cancer Immunol Immunother. 2022 Feb.

Abstract

Background: Cancer cachexia is a multifactorial syndrome characterized by weight loss leading to immune dysfunction that is commonly observed in patients with advanced non-small cell lung cancer (NSCLC). We examined the impact of cachexia on the prognosis of patients with advanced NSCLC receiving pembrolizumab and evaluated whether the pathogenesis of cancer cachexia affects the clinical outcome.

Patients and methods: Consecutive patients with advanced NSCLC treated with pembrolizumab were retrospectively enrolled in the study. Serum levels of pro-inflammatory cytokines and appetite-related hormones, which are related to the pathogenesis of cancer cachexia, were analyzed. Cancer cachexia was defined as (1) a body weight loss > 5% over the past 6 months, or (2) a body weight loss > 2% in patients with a body mass index < 20 kg/m2.

Results: A total of 133 patients were enrolled. Patients with cachexia accounted for 35.3%. No significant difference in the objective response rate was seen between the cachexia and non-cachexia group (29.8% vs. 34.9%, P = 0.550), but the median progression-free survival (PFS) and overall survival (OS) periods were significantly shorter in the cachexia group than in the non-cachexia group (PFS: 4.2 months vs. 7.1 months, P = 0.04, and OS: 10.0 months vs. 26.6 months, P = 0.03). The serum TNF-alpha, IL-1 alpha, IL-8, IL-10, and leptin levels were significantly associated with the presence of cachexia, but not with the PFS or OS.

Conclusion: The presence of cachexia was significantly associated with poor prognosis in advanced NSCLC patients receiving pembrolizumab, not with the response to pembrolizumab.

Keywords: Cancer cachexia; Ghrelin; Leptin; Non-small cell lung cancer; Pembrolizumab; Pro-inflammatory cytokine.

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Conflict of interest statement

HJ has nothing to disclose. TY reports grants from ONO Pharmaceutical, during the conduct of the study; grants and personal fees from AstraZeneca, grants and personal fees from Bristol Myers Squibb, grants from Takeda, personal fees from Chugai, personal fees from Novartis, grants from MSD, grants from AbbVie, outside the submitted work; HH reports grants and personal fees from BMS, grants and personal fees from MSD, grants and personal fees from Chugai, grants and personal fees from Taiho, grants and personal fees from AstraZeneca, grants from Astellas, grants from Merck Serono, grants from Genomic Health, grants and personal fees from Lilly, grants and personal fees from Ono, outside the submitted work; SY has grants from Nippon Boehringer Ingelheim. YM reports grants from National Cancer Center Research and Development Fund, grants from Grant-in-Aid for Scientific Research on Innovative Areas, grants from Hitachi, Ltd., grants from Hitachi High-Technologies, personal fees from Olympus, personal fees from AstraZeneca, personal fees from Novartis, personal fees from COOK, personal fees from AMCO INC., outside the submitted work; YS has nothing to disclose. YO reports personal fees from AstraZeneca K.K., personal fees from Nippon Boehringer Ingelheim, personal fees from Eli Lilly K.K., personal fees from MSD K.K., personal fees from Chugai Pharma Co., Ltd, personal fees from Ono Pharma Co., Ltd, personal fees from Bristol Myers Squibb, outside the submitted work; YG reports grants and personal fees from Eli Lilly, grants and personal fees from Chugai, grants and personal fees from Taiho Pharmaceutical, personal fees from Boehringer Ingelheim, grants and personal fees from Pfizer, grants and personal fees from Novartis, personal fees from AstraZeneca, grants and personal fees from MSD, grants and personal fees from Guardant Health, grants and personal fees from Ono Pharmaceutical, grants from Kyorin, grants from Daiichi Sankyo, personal fees from Illumina, outside the submitted work; NY reports grants from Chugai, grants from Taiho, grants from Eisai, grants from Lilly, grants from Quintiles, grants from Astellas, grants from BMS, grants from Novartis, grants from Daiichi Sankyo, grants from Pfizer, grants from Boehringer Ingelheim, grants from Kyowa Hakko Kirin, grants from Bayer, grants from ONO PHARMACEUTICAL CO., LTD, grants from Takeda, personal fees from ONO PHARMACEUTICAL CO., LTD, personal fees from Chugai, personal fees from AstraZeneca, personal fees from Pfizer, personal fees from Lilly, personal fees from BMS, personal fees from Eisai, personal fees from Otsuka, personal fees from Takeda, personal fees from Boehringer Ingelheim, personal fees from Cimic, grants from Janssen Pharma, grants from MSD, grants from Merck, personal fees from Sysmex, grants from GSK, grants from Sumitomo Dainippon, outside the submitted work; KT reports grants and personal fees from Chugai Pharmaceutical Co., Ltd., grants and personal fees from Nippon Boehringer lngelheim Co., Ltd., grants and personal fees from MSD K.K, grants from Glaxo SmithKline Consumer Healthcare Japan K.K, grants from NIPPON SHINYAKU CO., LTD., grants from TSUMURA & CO., grants and personal fees from Pfizer Inc., personal fees from AstraZeneca K.K, grants and personal fees from TAIHO PHARMACEUTICAL CO., LTD., grants from DAIICHI SANKYO Co., LTD., grants from Astellas Pharma Inc., grants and personal fees from KYORIN Pharmaceutical Co., Ltd., grants from KYOWA Hakko Kirin Co., Ltd., grants from TEIJIN PHARMA LIMITED, grants from Sanofi K.K., grants and personal fees from ONO PHARMACEUTICAL CO., LTD., grants from Shionogi & Co., Ltd., personal fees from Bristol Myers Squibb Company, grants and personal fees from Novartis Pharma K.K, grants and personal fees from Eli Lilly Japan K.K, grants from Actelion Pharmaceuticals Japan Ltd., grants from NIPRO PHARMA CORPORATION, grants from Astellas Pharma lnc., grants from Takeda Pharmaceutical Company Limited., grants from Bayer Yakuhin, Ltd, grants from Torii Pharmaceutical Co., Ltd, personal fees from MSD K.K, personal fees from Meiji Seika Pharma Co, Ltd., outside the submitted work; NM reports grants and personal fees from Ono, personal fees from BMS, personal fees from MSD, personal fees from AstraZeneca, grants and personal fees from Roche Diagnostics, personal fees from Novartis, personal fees from Taiho, personal fees from Chugai, personal fees from Miraca Life Science, personal fees from Beckton Dickinson Japan, personal fees from Covidien Japan Inc, outside the submitted work; YO reports grants and personal fees from AstraZeneca, grants and personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, grants and personal fees from Chugai, personal fees from Celltrion, personal fees from Amgen, grants and personal fees from Eli Lilly, from Janssen, grants and personal fees from Kyorin, grants and personal fees from Nippon Kayaku, grants and personal fees from Novartis, grants and personal fees from ONO Pharmaceutical, grants and personal fees from Pfizer, grants from Ignyta, grants and personal fees from Taiho, grants and personal fees from Takeda, outside the submitted work.

Figures

Fig. 1
Fig. 1
Flow diagram of the study
Fig. 2
Fig. 2
a Objective responses, b progression-free survival and c overall survival for patients treated with pembrolizumab in the cachexia (N = 47) and the non-cachexia (N = 86) groups. d Best responses (PR or CR and SD or PD) in the body weight recovered (N = 12) and the not recovered (N = 20) groups. e Duration of response in the body weight recovered (N = 10) and not recovered (N = 3) groups among patients with CR or PR. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, objective response rate; DCR, disease control rate; NR, not reached. P value was calculated by comparing the recovered and the not recovered groups
Fig. 3
Fig. 3
Correlations of serum pro-inflammatory cytokine and appetite-related hormone levels with cachexia (N = 116). TNF-α, tumor necrosis factor-α; IL, interleukin. P values were calculated by comparing the cachexia and the non-cachexia groups
Fig. 4
Fig. 4
Analyses of patient survival and frequency of cachexia according to ghrelin and leptin levels. a Kaplan–Meier curves for overall survival for four groups by classified according to ghrelin and leptin levels. b Proportion of patients with cachexia in the four groups classified according to ghrelin and leptin levels. Low G, low ghrelin level; low L, low leptin level; high G, high ghrelin level; high L, high leptin level. *P values were calculated by comparing the high G, low L group with the rest
See this image and copyright information in PMC

References

    1. Aoyagi T, Terracina KP, Raza A, et al. Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol. 2015;7(4):17–29. doi: 10.4251/wjgo.v7.i4.17. - DOI - PMC - PubMed
    1. Argiles JM, Busquets S, Stemmler B, et al. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–762. doi: 10.1038/nrc3829. - DOI - PubMed
    1. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–495. doi: 10.1016/s1470-2045(10)70218-7. - DOI - PubMed
    1. Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012;16(2):153–166. doi: 10.1016/j.cmet.2012.06.011. - DOI - PubMed
    1. Baracos VE, Martin L, Korc M, et al. Cancer-associated cachexia. Nat Rev Dis Primers. 2018;4:17105. doi: 10.1038/nrdp.2017.105. - DOI - PubMed

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