Use of Antibiotics during Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Hepatocellular Carcinoma

被引:44
作者
Cheung, Ka Shing [1 ,2 ]
Lam, Lok Ka [1 ]
Seto, Wai Kay [1 ,2 ]
Leung, Wai K. [1 ]
机构
[1] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Peoples R China
[2] Univ Hong Kong, Shenzhen Hosp, Dept Med, Shenzhen, Peoples R China
关键词
Immunology; Liver cancer; Cirrhosis; Hepatocellular carcinoma; PD-1; BLOCKADE; EFFICACY;
D O I
10.1159/000518090
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Recent studies suggested that use of antibiotics may interfere with treatment responses to immune checkpoint inhibitors (ICIs). We determined whether concurrent use of antibiotics during ICI therapy was associated with adverse outcomes in patients with advanced hepatocellular carcinoma (HCC). Methods: This is a territory-wide retrospective cohort study including all advanced HCC patients who received ICIs (nivolumab, pembrolizumab, or ipilimumab) between January 2014 and December 2019. Exclusion criteria included prior liver transplantation and use of cabozantinib, regorafenib, or ramucirumab. The exposure of interest was concurrent antibiotic use within 30 days before or after the commencement of ICI. The adjusted hazard ratio (aHR) of cancer-related mortality and all-cause mortality with antibiotic use was derived by propensity score (PS) matching in 1:2 ratio of covariates including baseline characteristics, causes of cirrhosis, Child-Pugh status, prior HCC treatment, comorbidities, concurrent medications, and laboratory results including alpha fetoprotein. Results: A total of 395 HCC patients who had received ICIs were included. During a median follow-up of 16.5 months (interquartile range [IQR]: 5.6-44.3), there were 286 (72.4%) deaths including 231 cancer-related deaths. The median time from the first ICI to event was 7.7 months (IQR: 4.0-16.8). PS matching of 56 antibiotic users with 99 nonusers showed that concurrent antibiotic use with ICI was associated with higher cancer-related (aHR: 1.66; 95% CI: 1.08-2.54) and all-cause mortality (aHR: 1.63; 95% CI: 1.17-2.28). Conclusions: Concurrent antibiotic use during immunotherapy was associated with higher mortality in patients with advanced HCC. Further studies should examine the role of gut dysbiosis on responses to ICI.
引用
收藏
页码:606 / 614
页数:9
相关论文
共 27 条
  • [1] Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples
    Austin, Peter C.
    [J]. STATISTICS IN MEDICINE, 2009, 28 (25) : 3083 - 3107
  • [2] Chalabi M, 2020, ANN ONCOL, V31, P525, DOI [10.1016/j.annoc.2020.01.006, 10.1016/j.annonc.2020.01.006]
  • [3] Diabetes Increases Risk of Gastric Cancer After Helicobacter pylori Eradication: A Territory-Wide Study With Propensity Score Analysis
    Cheung, Ka Shing
    Chan, Esther W.
    Chen, Lijia
    Seto, Wai Kay
    Wong, Ian C. K.
    Leung, Wai K.
    [J]. DIABETES CARE, 2019, 42 (09) : 1769 - 1775
  • [4] Application of Big Data analysis in gastrointestinal research
    Cheung, Ka-Shing
    Leung, Wai K.
    Seto, Wai-Kay
    [J]. WORLD JOURNAL OF GASTROENTEROLOGY, 2019, 25 (24) : 2990 - 3008
  • [5] Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187 897 patients
    Cheung, Ka-Shing
    Chen, Lijia
    Chan, Esther W.
    Seto, Wai-Kay
    Wong, Ian C. K.
    Leung, Wai K.
    [J]. GUT, 2019, 68 (11) : 1979 - 1985
  • [6] Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016
    Cheung, Ka-Shing
    Seto, Wai-Kay
    Fung, James
    Mak, Lung-Yi
    Lai, Ching-Lung
    Yuen, Man-Fung
    [J]. WORLD JOURNAL OF GASTROENTEROLOGY, 2017, 23 (43) : 7716 - 7726
  • [7] Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer
    Derosa, L.
    Hellmann, M. D.
    Spaziano, M.
    Halpenny, D.
    Fidelle, M.
    Rizvi, H.
    Long, N.
    Plodkowski, A. J.
    Arbour, K. C.
    Chaft, J. E.
    Rouche, J. A.
    Zitvogel, L.
    Zalcman, G.
    Albiges, L.
    Escudier, B.
    Routy, B.
    [J]. ANNALS OF ONCOLOGY, 2018, 29 (06) : 1437 - 1444
  • [8] Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial
    El-Khoueiry, Anthony B.
    Sangro, Bruno
    Yau, Thomas
    Crocenzi, Todd S.
    Kudo, Masatoshi
    Hsu, Chiun
    Kim, Tae-You
    Choo, Su-Pin
    Trojan, Jorg
    Welling, Theodore H., III
    Meyer, Tim
    Kang, Yoon-Koo
    Yeo, Winnie
    Chopra, Akhil
    Anderson, Jeffrey
    dela Cruz, Christine
    Lang, Lixin
    Neely, Jaclyn
    Tang, Hao
    Dastani, Homa B.
    Melero, Ignacio
    [J]. LANCET, 2017, 389 (10088) : 2492 - 2502
  • [9] Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
    Gopalakrishnan, V.
    Spencer, C. N.
    Nezi, L.
    Reuben, A.
    Andrews, M. C.
    Karpinets, T. V.
    Prieto, P. A.
    Vicente, D.
    Hoffman, K.
    Wei, S. C.
    Cogdill, A. P.
    Zhao, L.
    Hudgens, C. W.
    Hutchinson, D. S.
    Manzo, T.
    de Macedo, M. Petaccia
    Cotechini, T.
    Kumar, T.
    Chen, W. S.
    Reddy, S. M.
    Sloane, R. Szczepaniak
    Galloway-Pena, J.
    Jiang, H.
    Chen, P. L.
    Shpall, E. J.
    Rezvani, K.
    Alousi, A. M.
    Chemaly, R. F.
    Shelburne, S.
    Vence, L. M.
    Okhuysen, P. C.
    Jensen, V. B.
    Swennes, A. G.
    McAllister, F.
    Sanchez, E. Marcelo Riquelme
    Zhang, Y.
    Le Chatelier, E.
    Zitvogel, L.
    Pons, N.
    Austin-Breneman, J. L.
    Haydu, L. E.
    Burton, E. M.
    Gardner, J. M.
    Sirmans, E.
    Hu, J.
    Lazar, A. J.
    Tsujikawa, T.
    Diab, A.
    Tawbi, H.
    Glitza, I. C.
    [J]. SCIENCE, 2018, 359 (6371) : 97 - 103
  • [10] T-cell invigoration to tumour burden ratio associated with anti-PD-1 response
    Huang, Alexander C.
    Postow, Michael A.
    Orlowski, Robert J.
    Mick, Rosemarie
    Bengsch, Bertram
    Manne, Sasikanth
    Xu, Wei
    Harmon, Shannon
    Giles, Josephine R.
    Wenz, Brandon
    Adamow, Matthew
    Kuk, Deborah
    Panageas, Katherine S.
    Carrera, Cristina
    Wong, Phillip
    Quagliarello, Felix
    Wubbenhorst, Bradley
    D'Andrea, Kurt
    Pauken, Kristen E.
    Herati, Ramin S.
    Staupe, Ryan P.
    Schenkel, Jason M.
    McGettigan, Suzanne
    Kothari, Shawn
    George, Sangeeth M.
    Vonderheide, Robert H.
    Amaravadi, Ravi K.
    Karakousis, Giorgos C. .
    Schuchter, Lynn M.
    Xu, Xiaowei
    Nathanson, Katherine L.
    Wolchok, Jedd D.
    Gangadhar, Tara C.
    Wherry, E. John
    [J]. NATURE, 2017, 545 (7652) : 60 - +