Impact of Antibiotic Exposure Before Immune Checkpoint Inhibitor Treatment on Overall Survival in Older Adults With Cancer: A Population-Based Study

被引:34
作者
Eng, Lawson [1 ,2 ]
Sutradhar, Rinku [3 ,4 ]
Niu, Yue [3 ]
Liu, Ning [3 ]
Liu, Ying [3 ]
Kaliwal, Yosuf [3 ]
Powis, Melanie L. [1 ]
Liu, Geoffrey [1 ,2 ]
Peppercorn, Jeffrey M. [5 ]
Bedard, Philippe L. [1 ,2 ]
Krzyzanowska, Monika K. [1 ,2 ,3 ]
机构
[1] Univ Hlth Network, Princess Margaret Canc Ctr, Dept Med, 1Divis Med Oncol & Hematol, Toronto, ON, Canada
[2] Univ Toronto, Dept Med, 2Divison Med Oncol, Toronto, ON, Canada
[3] Inst Clin Evaluat Sci, Res Program 3Cancer, Toronto, ON, Canada
[4] Univ Toronto, Dalla Lana Sch Publ Hlth, 4Divis Biostat, Toronto, ON, Canada
[5] Massachusetts Gen Hosp, Harvard Med Sch, 5Divis Hematol-Oncol, Boston, MA USA
关键词
2ND-LINE THERAPY; SYSTEMIC THERAPY; OPEN-LABEL; NIVOLUMAB; PEMBROLIZUMAB; IMMUNOTHERAPY; CARCINOMA; MELANOMA; OUTCOMES; CHEMOTHERAPY;
D O I
10.1200/JCO.22.00074
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PURPOSEAntibiotic exposure before immune checkpoint inhibitor (ICI) treatment can negatively affect outcomes through alteration in the gut microbiome, but large-scale evaluations are lacking. We performed a population-level retrospective cohort study to evaluate the impact of antibiotic exposure before starting ICI on overall survival (OS).PATIENT AND METHODSPatients with cancer, age 65 years or older, who initiated treatment with ICIs between June 2012 and October 2018 in Ontario, Canada, were identified using systemic therapy administration data. The cohort was deterministically linked to other health care databases to obtain covariates and antibiotic prescription claim data at both 1 year and 60 days before ICI therapy. Multivariable Cox models evaluated the association between exposure and OS.RESULTSAmong the 2,737 patients with cancer who received ICIs, 59% and 19% of patients received antibiotics 1 year and 60 days before ICI therapy, respectively. Median OS was 306 days. Any antibiotic exposure within 1 year before ICI was associated with worse OS (adjusted hazard ratio [aHR], 1.12; 95% CI, 1.12 to 1.23; P = .03). In antibiotic class analysis, exposure to fluoroquinolones within 1 year (aHR, 1.26; 95% CI, 1.13 to 1.40; P < .001) or 60 days before ICI (aHR, 1.20; 95% CI, 0.99 to 1.45; P = .06) was associated with worse OS, with a dose effect seen on the basis of total weeks of exposure over 1 year (aHR, 1.07 per week; 95% CI, 1.03 to 1.11; P < .001) and 60 days (aHR, 1.12 per week; 95% CI, 1.03 to 1.23; P = .01).CONCLUSIONIn this population-level study, exposure to antibiotics and specifically fluoroquinolones before ICI therapy was observed to be associated with worse OS among older adults with cancer. Interventions aimed at altering the gut microbiome to boost immunogenicity may help improve outcomes for patients receiving ICIs with prior antibiotic exposure.
引用
收藏
页码:3122 / +
页数:20
相关论文
共 58 条
  • [1] [Anonymous], 2020, ONT HLTH CANC CAR ON
  • [2] Avelumab, an Anti-Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study
    Apolo, Andrea B.
    Infante, Jeffrey R.
    Balmanoukian, Ani
    Patel, Manish R.
    Wang, Ding
    Kelly, Karen
    Mega, Anthony E.
    Britten, Carolyn D.
    Ravaud, Alain
    Mita, Alain C.
    Safran, Howard
    Stinchcombe, Thomas E.
    Srdanov, Marko
    Gelb, Arnold B.
    Schlichting, Michael
    Chin, Kevin
    Gulley, James L.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (19) : 2117 - +
  • [3] Bugs as drugs: The role of microbiome in cancer focusing on immunotherapeutics
    Araujo, Daniel, V
    Watson, Geoffrey A.
    Oliva, Marc
    Heirali, Alya
    Coburn, Bryan
    Spreafico, Anna
    Siu, Lillian L.
    [J]. CANCER TREATMENT REVIEWS, 2021, 92
  • [4] Using the Johns Hopkins Aggregated Diagnosis Groups (ADGs) to Predict Mortality in a General Adult Population Cohort in Ontario, Canada
    Austin, Peter C.
    van Walraven, Carl
    Wodchis, Walter P.
    Newman, Alice
    Anderson, Geoffrey M.
    [J]. MEDICAL CARE, 2011, 49 (10) : 932 - 939
  • [5] Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma
    Bellmunt, J.
    de Wit, R.
    Vaughn, D. J.
    Fradet, Y.
    Lee, J. -L.
    Fong, L.
    Vogelzang, N. J.
    Climent, M. A.
    Petrylak, D. P.
    Choueiri, T. K.
    Necchi, A.
    Gerritsen, W.
    Gurney, H.
    Quinn, D. I.
    Culine, S.
    Sternberg, C. N.
    Mai, Y.
    Poehlein, C. H.
    Perini, R. F.
    Bajorin, D. F.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (11) : 1015 - 1026
  • [6] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer
    Borghaei, H.
    Paz-Ares, L.
    Horn, L.
    Spigel, D. R.
    Steins, M.
    Ready, N. E.
    Chow, L. Q.
    Vokes, E. E.
    Felip, E.
    Holgado, E.
    Barlesi, F.
    Kohlhaeufl, M.
    Arrieta, O.
    Burgio, M. A.
    Fayette, J.
    Lena, H.
    Poddubskaya, E.
    Gerber, D. E.
    Gettinger, S. N.
    Rudin, C. M.
    Rizvi, N.
    Crino, L.
    Blumenschein, G. R.
    Antonia, S. J.
    Dorange, C.
    Harbison, C. T.
    Finckenstein, F. Graf
    Brahmer, J. R.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) : 1627 - 1639
  • [7] Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab
    Chaput, N.
    Lepage, P.
    Coutzac, C.
    Soularue, E.
    Le Roux, K.
    Monot, C.
    Boselli, L.
    Routier, E.
    Cassard, L.
    Collins, M.
    Vaysse, T.
    Marthey, L.
    Eggermont, A.
    Asvatourian, V.
    Lanoy, E.
    Mateus, C.
    Robert, C.
    Carbonnel, F.
    [J]. ANNALS OF ONCOLOGY, 2017, 28 (06) : 1368 - 1379
  • [8] Describing the linkages of the immigration, refugees and citizenship Canada permanent resident data and vital statistics death registry to Ontario's administrative health database
    Chiu, Maria
    Lebenbaum, Michael
    Lam, Kelvin
    Chong, Nelson
    Azimaee, Mahmoud
    Iron, Karey
    Manuel, Doug
    Guttmann, Astrid
    [J]. BMC MEDICAL INFORMATICS AND DECISION MAKING, 2016, 16
  • [9] Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy
    Cortellini, A.
    Ricciuti, B.
    Facchinetti, F.
    Alessi, J. V. M.
    Venkatraman, D.
    Dall'Olio, F. G.
    Cravero, P.
    Vaz, V. R.
    Ottaviani, D.
    Majem, M.
    Piedra, A.
    Sullivan, I
    Lee, K. A.
    Lamberti, G.
    Hussain, N.
    Clark, J.
    Bolina, A.
    Barba, A.
    Benitez, J. C.
    Gorria, T.
    Mezquita, L.
    Hoton, D.
    Nana, F. Aboubakar
    Besse, B.
    Awad, M. M.
    Pinato, D. J.
    [J]. ANNALS OF ONCOLOGY, 2021, 32 (11) : 1391 - 1399
  • [10] Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy
    Cristescu, Razvan
    Mogg, Robin
    Ayers, Mark
    Albright, Andrew
    Murphy, Erin
    Yearley, Jennifer
    Sher, Xinwei
    Liu, Xiao Qiao
    Lu, Hongchao
    Nebozhyn, Michael
    Zhang, Chunsheng
    Lunceford, Jared
    Joe, Andrew
    Cheng, Jonathan
    Webber, Andrea L.
    Ibrahim, Nageatte
    Plimack, Elizabeth R.
    Ott, Patrick A.
    Seiwert, Tanguy
    Ribas, Antoni
    McClanahan, Terrill K.
    Tomassini, Joanne E.
    Loboda, Andrey
    Kaufman, David
    [J]. SCIENCE, 2018, 362 (6411) : 197 - +