PLoS ONE (Jan 2023)

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

  • Kazuki Maesaka,
  • Ryotaro Sakamori,
  • Ryoko Yamada,
  • Akira Doi,
  • Yuki Tahata,
  • Kazuyoshi Ohkawa,
  • Masahide Oshita,
  • Masanori Miyazaki,
  • Takayuki Yakushijin,
  • Yasutoshi Nozaki,
  • Kengo Matsumoto,
  • Satoshi Tanaka,
  • Akira Kaneko,
  • Sadaharu Iio,
  • Takatoshi Nawa,
  • Yukinori Yamada,
  • Naoki Morishita,
  • Takeo Usui,
  • Naoki Hiramatsu,
  • Yoshinori Doi,
  • Mitsuru Sakakibara,
  • Kazuho Imanaka,
  • Yuichi Yoshida,
  • Takahiro Kodama,
  • Hayato Hikita,
  • Tomohide Tatsumi,
  • Tetsuo Takehara

DOI
https://doi.org/10.1371/journal.pone.0281459
Journal volume & issue
Vol. 18, no. 2
p. e0281459

Abstract

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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.