Pretreatment with antibiotics is associated with reduced therapeutic response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma

被引：10

作者：

Maesaka, Kazuki ^{[1
]}

Sakamori, Ryotaro ^{[1
]}

Yamada, Ryoko ^{[1
]}

Doi, Akira ^{[1
]}

Tahata, Yuki ^{[1
]}

Ohkawa, Kazuyoshi ^{[2
]}

Oshita, Masahide ^{[3
]}

Miyazaki, Masanori ^{[4
]}

Yakushijin, Takayuki ^{[5
]}

Nozaki, Yasutoshi ^{[6
]}

Matsumoto, Kengo ^{[7
]}

Tanaka, Satoshi ^{[8
]}

Kaneko, Akira ^{[9
]}

Iio, Sadaharu ^{[10
]}

Nawa, Takatoshi ^{[11
]}

Yamada, Yukinori ^{[12
]}

Morishita, Naoki ^{[13
]}

Usui, Takeo ^{[14
]}

Hiramatsu, Naoki ^{[15
]}

Doi, Yoshinori ^{[16
]}

Sakakibara, Mitsuru ^{[17
]}

Imanaka, Kazuho ^{[18
]}

Yoshida, Yuichi ^{[19
]}

Kodama, Takahiro ^{[1
]}

Hikita, Hayato ^{[1
]}

Tatsumi, Tomohide ^{[1
]}

Takehara, Tetsuo ^{[1
]}

机构：

[1] Osaka Univ, Dept Gastroenterol & Hepatol, Grad Sch Med, Suita, Osaka, Japan

[2] Osaka Int Canc Inst, Dept Hepatobiliary & Pancreat Oncol, Osaka, Osaka, Japan

[3] Ikeda Municipal Hosp, Dept Gastroenterol & Hepatol, Ikeda, Osaka, Japan

[4] Osaka Police Hosp, Dept Gastroenterol & Hepatol, Osaka, Osaka, Japan

[5] Osaka Gen Med Ctr, Dept Gastroenterol & Hepatol, Osaka, Osaka, Japan

[6] Kansai Rosai Hosp, Dept Gastroenterol & Hepatol, Amagasaki, Hyogo, Japan

[7] Toyonaka City Hosp, Dept Gastroenterol & Hepatol, Toyonaka, Osaka, Japan

[8] Natl Hosp Org Osaka Natl Hosp, Dept Gastroenterol & Hepatol, Osaka, Osaka, Japan

[9] Osaka Hosp, Japan Community Healthcare Org, Dept Gastroenterol & Hepatol, Osaka, Osaka, Japan

[10] Hyogo Prefectural Nishinomiya Hosp, Dept Gastroenterol & Hepatol, Nishinomiya, Hyogo, Japan

[11] Higashiosaka City Med Ctr, Dept Gastroenterol & Hepatol, Higashiosaka, Osaka, Japan

[12] Kaizuka City Hosp, Dept Gastroenterol & Hepatol, Kaizuka, Osaka, Japan

[13] Minoh City Hosp, Dept Gastroenterol & Hepatol, Osaka, Japan

[14] Ashiya Municipal Hosp, Dept Gastroenterol & Hepatol, Ashiya, Hyogo, Japan

[15] Osaka Rosai Hosp, Dept Gastroenterol & Hepatol, Sakai, Osaka, Japan

[16] Otemae Hosp, Dept Gastroenterol & Hepatol, Osaka, Osaka, Japan

[17] Yao Municipal Hosp, Dept Gastroenterol & Hepatol, Yao, Osaka, Japan

[18] Itami City Hosp, Dept Gastroenterol & Hepatol, Itami, Hyogo, Japan

[19] Suita Municipal Hosp, Dept Gastroenterol & Hepatol, Suita, Osaka, Japan

来源：

PLOS ONE | 2023年 / 18卷 / 02期

关键词：

PD-1; BLOCKADE; EFFICACY; IMMUNOTHERAPY; CHEMOTHERAPY; MICROBIOME; INHIBITORS;

D O I：

10.1371/journal.pone.0281459

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

AimAlterations in microbial composition of gut microbiota due to antibiotics (ATB) may lead to resistance to immune checkpoint inhibitors (ICIs). This study aimed to assess the impact of ATB use on therapeutic response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab. MethodsThis study retrospectively analyzed 105 patients with HCC treated with atezolizumab plus bevacizumab as a primary systemic therapy from prospectively-registered, multicenter, cohorts. Nineteen patients who received prior ATB were included in the ATB (+) group; 86 patients who did not receive prior ATB were included in the ATB (-) group. The therapeutic outcomes were compared between the two groups. ResultsMost of the patients' baseline characteristics were not significantly different between the two groups. The objective response rates according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (30.1% vs. 11.1%; p = 0.143) and modified RECIST (mRECIST) (44.6% vs. 27.8%; p = 0.190) were not significantly different between the ATB (-) and ATB (+) groups. The disease control rates were higher in the ATB (-) group than in the ATB (+) group according to RECIST v1.1 (74.7% vs. 44.4%; p = 0.012) and mRECIST (78.3% vs. 50.0%; p = 0.020). Prior ATB use was found to be independently associated with radiological progressive disease of the first therapeutic assessment. The median progression-free survival according to RECIST v1.1 (9.1 months vs. 3.0 months; p = 0.049) and mRECIST (9.1 months vs. 3.0 months; p = 0.036), and overall survival (not reached vs. 11.4 months; p = 0.015) were longer in the ATB (-) group than in the ATB (+) group. ConclusionsPrior ATB use was associated with reduced therapeutic responses in patients with HCC receiving atezolizumab plus bevacizumab.

引用

页数：15

共 41 条

[1] IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade [J].

Ayers, Mark ;

Lunceford, Jared ;

Nebozhyn, Michael ;

Murphy, Erin ;

Loboda, Andrey ;

Kaufman, David R. ;

Albright, Andrew ;

Cheng, Jonathan D. ;

Kang, S. Peter ;

Shankaran, Veena ;

Piha-Paul, Sarina A. ;

Yearley, Jennifer ;

Seiwert, Tanguy Y. ;

Ribas, Antoni ;

McClanahan, Terrill K. .

JOURNAL OF CLINICAL INVESTIGATION, 2017, 127 (08) :2930-2940

[2] Antibiotic-Induced Changes in the Intestinal Microbiota and Disease [J].

Becattini, Simone ;

Taur, Ying ;

Pamer, Eric G. .

TRENDS IN MOLECULAR MEDICINE, 2016, 22 (06) :458-478

[3] Systemic treatment of hepatocellular carcinoma: An EASL position paper [J].

Bruix, Jordi ;

Chan, Stephen L. ;

Galle, Peter R. ;

Rimassa, Lorenza ;

Sangro, Bruno .

JOURNAL OF HEPATOLOGY, 2021, 75 (04) :960-974

[4]

Chalabi M, 2020, ANN ONCOL, V31, P525, DOI [10.1016/j.annonc.2020.01.006, 10.1016/j.annoc.2020.01.006]

[5]

Cheng AL, 2022, J HEPATOL, V76, P862, DOI [10.1016/j.jhep.2021.11.030, 10.1016/j.jceh.2022.07.003]

[6] Use of Antibiotics during Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Hepatocellular Carcinoma [J].

Cheung, Ka Shing ;

Lam, Lok Ka ;

Seto, Wai Kay ;

Leung, Wai K. .

LIVER CANCER, 2021, 10 (06) :606-614

[7] Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy [J].

Cortellini, Alessio ;

Di Maio, Massimo ;

Nigro, Olga ;

Leonetti, Alessandro ;

Cortinovis, Diego L. ;

Aerts, Joachim G. J., V ;

Guaitoli, Giorgia ;

Barbieri, Fausto ;

Giusti, Raffaele ;

Ferrara, Miriam G. ;

Bria, Emilio ;

D'Argento, Ettore ;

Grossi, Francesco ;

Rijavec, Erika ;

Guida, Annalisa ;

Berardi, Rossana ;

Torniai, Mariangela ;

Sforza, Vincenzo ;

Genova, Carlo ;

Mazzoni, Francesca ;

Garassino, Marina Chiara ;

De Toma, Alessandro ;

Signorelli, Diego ;

Gelibter, Alain ;

Siringo, Marco ;

Marchetti, Paolo ;

Macerelli, Marianna ;

Rastelli, Francesca ;

Chiari, Rita ;

Rocco, Danilo ;

Della Gravara, Luigi ;

Inno, Alessandro ;

Michele, De Tursi ;

Grassadonia, Antonino ;

Di Marino, Pietro ;

Mansueto, Giovanni ;

Zoratto, Federica ;

Filetti, Marco ;

Santini, Daniele ;

Citarella, Fabrizio ;

Russano, Marco ;

Cantini, Luca ;

Tuzi, Alessandro ;

Bordi, Paola ;

Minuti, Gabriele ;

Landi, Lorenza ;

Ricciardi, Serena ;

Migliorino, Maria R. ;

Passiglia, Francesco ;

Bironzo, Paolo .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2021, 9 (04)

[8] Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer [J].

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. .

ANNALS OF ONCOLOGY, 2018, 29 (06) :1437-1444

[9] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

[10] Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma [J].

Fessas, Petros ;

Naeem, Muntaha ;

Pinter, Matthias ;

Marron, Thomas U. ;

Szafron, David ;

Balcar, Lorenz ;

Saeed, Anwaar ;

Jun, Tomi ;

Dharmapuri, Sirish ;

Gampa, Anuhya ;

Wang, Yinghong ;

Khan, Uqba ;

Muzaffar, Mahvish ;

Navaid, Musharraf ;

Lee, Pei-Chang ;

Bulumulle, Anushi ;

Yu, Bo ;

Paul, Sonal ;

Nimkar, Neil ;

Bettinger, Dominik ;

Hildebrand, Hannah ;

Abugabal, Yehia, I ;

Pressiani, Tiziana ;

Personeni, Nicola ;

Nishida, Naoshi ;

Kudo, Masatoshi ;

Kaseb, Ahmed ;

Huang, Yi-Hsiang ;

Ang, Celina ;

Pillai, Anjana ;

Rimassa, Lorenza ;

Naqash, Abdul Rafeh ;

Sharon, Elad ;

Cortellini, Alessio ;

Pinato, David J. .

LIVER CANCER, 2021, 10 (06) :583-592

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