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Article

Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma

  • Authors:
    • Nobuaki Ishihara
    • Shohei Komatsu
    • Yoshihiko Yano
    • Yoshimi Fujishima
    • Jun Ishida
    • Masahiro Kido
    • Hidetoshi Gon
    • Kenji Fukushima
    • Takeshi Urade
    • Hiroaki Yanagimoto
    • Hirochika Toyama
    • Yuzo Kodama
    • Takumi Fukumoto
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Division of Hepato‑Biliary‑Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Department of Internal Medicine, Division of Gastroenterology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Division of Oncology, Kobe Minimally invasive Cancer Center, Kobe, Hyogo 650‑0046, Japan, Division of Radiology, Kobe Minimally invasive Cancer Center, Kobe, Hyogo 650‑0046, Japan
  • Article Number: 466
    |
    Published online on: July 31, 2025
       https://doi.org/10.3892/ol.2025.15212
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Abstract

Atezolizumab plus bevacizumab (AteBev) is used as a first‑line treatment for advanced hepatocellular carcinoma (HCC). Combining AteBev with sequential local treatment holds potential; however, optimal timing, modality and continuation of systemic chemotherapy remain undetermined. In the present study, a retrospective analysis of 123 patients with HCC treated with AteBev at two institutions was performed. Patients with no apparent residual lesions after sequential local treatment or AteBev treatment alone were followed up without any systemic chemotherapy (‘drug‑free’ cohort). Outcomes focused on the impact of achieving ‘drug‑free’ status, with timing assessed based on tumor size and α‑fetoprotein levels. The results revealed that serum α‑fetoprotein levels and tumor shrinkage plateaued at ~3 and 6 months post‑AteBev treatment, respectively. Patients achieving ‘drug‑free’ status demonstrated prolonged median survival (P<0.001) and progression‑free survival (P<0.001), comparable with patients with ‘clinical complete response’ or ‘drug‑off’ statuses. Moreover, particle radiotherapy was the most common local treatment modality. In conclusion, achieving a ‘drug‑free’ status was associated with favorable prognoses. Optimal timing for sequential local treatment is suggested as 3‑6 months after AteBev initiation, with multidisciplinary strategies to achieve ‘drug‑free’ status offering a promising option for the treatment of advanced HCC.
View Figures

Figure 1

OS and PFS analyzed using the
Kaplan-Meier method. (A) OS and (B) PFS of all patients. MST of all
patients was 21.7 months (95% CI, 15.9–25.4) and median PFS of all
patients is 7.4 months (95% CI, 5.0–10.2). (C) OS and (D) PFS
stratified by treatment response according to the RECIST (version
1.1). MST of each response category was as follows: CR, not reached
(95% CI, NA-NA); PR, 31.1 months (95% CI, 23.3-NA); SD, 15.9 months
(95% CI, 12.1–19.4); and PD, 11.6 months (95% CI, 7.0-NA). Median
PFS of each response category was as follows: CR, not reached (95%
CI, NA-NA); PR, 16.9 months (95% CI, 9.7–21.0); SD, 7.1 months (95%
CI, 4.4–9.7); and PD, 2.2 months (95% CI, 1.6–2.5). (E) OS and (F)
PFS of patients with or without an objective response according to
the RECIST (version 1.1). MST of patients with or without an
objective response is as follows: CR + PR, not reached (95% CI,
24.5-NA); and SD + PD, 15.0 months (95% CI, 11.9–18.9). Median PFS
of patients with or without an objective response was as follows:
CR + PR, 20.5 months (95% CI, 14.1-NA); and SD + PD, 4.1 months
(95% CI, 3.1–5.5). OS, overall survival; PFS, progression-free
survival; MST, median survival time; CI, confidence interval;
RECIST, Response Evaluation Criteria in Solid Tumors; CR, complete
response; NA, not applicable; PR, partial response; SD, stable
disease; PD, progressive disease.

Figure 2

Spider plots demonstrating the change
in the sum of tumor size in all patients during AteBev treatment.
Red lines indicate the patients who achieved sequential local
treatment after AteBev treatment. AteBev, atezolizumab plus
bevacizumab.

Figure 3

Transition of serum AFP levels during
AteBev treatment. Patients with serum AFP levels of ≥10 ng/ml,
which decreased at the first evaluation, were included in the
analysis. (A) Serum AFP ratio: AFP (X month)/AFP (before AteBev
initiation). (B) Serum AFP ratio: AFP (X month)/AFP (X-1 month).
AFP, α-fetoprotein; AteBev, atezolizumab plus bevacizumab.

Figure 4

OS and PFS analyzed using the
Kaplan-Meier method. (A) OS and (B) PFS of patients in the
‘drug-free’ cohort. MST of patients with or without ‘drug-free’
status was as follows: Drug-free (+), not reached (95% CI, 25.4-NA)
and drug-free (−), 16.3 months (95% CI, 13.0–21.8). Median PFS of
patients with or without ‘drug-free’ status was as follows:
Drug-free (+), not reached (95% CI, 18.4-NA) and drug-free (−), 5.0
months (95% CI, 3.7–7.1). (C) OS and (D) PFS of patients meeting
the ‘clinical CR’ criteria. MST of patients meeting or not meeting
the ‘clinical CR’ criteria was as follows: Clinical CR (+), not
reached (95% CI, NA-NA) and clinical CR (−), 16.9 months (95% CI,
13.6–23.0). Median PFS of patients meeting or not meeting the
‘clinical CR’ criteria was as follows: Clinical CR (+), not reached
(95% CI, 18.4-NA) and clinical CR (−), 5.5 months (95% CI,
4.1–8.8). (E) OS and (F) PFS of patients meeting the ‘drug-off’
criteria. MST of patients meeting or not meeting the ‘drug-off’
criteria was as follows: Drug-off (+), not reached (95% CI, NA-NA)
and drug-off (−), 18.9 months (95% CI, 14.1–23.0). Median PFS of
patients meeting or not meeting the ‘drug-off’ criteria was as
follows: Drug-off (+), not reached (95% CI, NA-NA) and drug-off
(−), 6.0 months (95% CI, 4.1–8.9). OS, overall survival; PFS,
progression-free survival; MST, median survival time; CI,
confidence interval; NA, not applicable; CR, complete response.
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Copy and paste a formatted citation
Spandidos Publications style
Ishihara N, Komatsu S, Yano Y, Fujishima Y, Ishida J, Kido M, Gon H, Fukushima K, Urade T, Yanagimoto H, Yanagimoto H, et al: Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma. Oncol Lett 30: 466, 2025.
APA
Ishihara, N., Komatsu, S., Yano, Y., Fujishima, Y., Ishida, J., Kido, M. ... Fukumoto, T. (2025). Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma. Oncology Letters, 30, 466. https://doi.org/10.3892/ol.2025.15212
MLA
Ishihara, N., Komatsu, S., Yano, Y., Fujishima, Y., Ishida, J., Kido, M., Gon, H., Fukushima, K., Urade, T., Yanagimoto, H., Toyama, H., Kodama, Y., Fukumoto, T."Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma". Oncology Letters 30.4 (2025): 466.
Chicago
Ishihara, N., Komatsu, S., Yano, Y., Fujishima, Y., Ishida, J., Kido, M., Gon, H., Fukushima, K., Urade, T., Yanagimoto, H., Toyama, H., Kodama, Y., Fukumoto, T."Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma". Oncology Letters 30, no. 4 (2025): 466. https://doi.org/10.3892/ol.2025.15212
Copy and paste a formatted citation
x
Spandidos Publications style
Ishihara N, Komatsu S, Yano Y, Fujishima Y, Ishida J, Kido M, Gon H, Fukushima K, Urade T, Yanagimoto H, Yanagimoto H, et al: Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma. Oncol Lett 30: 466, 2025.
APA
Ishihara, N., Komatsu, S., Yano, Y., Fujishima, Y., Ishida, J., Kido, M. ... Fukumoto, T. (2025). Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma. Oncology Letters, 30, 466. https://doi.org/10.3892/ol.2025.15212
MLA
Ishihara, N., Komatsu, S., Yano, Y., Fujishima, Y., Ishida, J., Kido, M., Gon, H., Fukushima, K., Urade, T., Yanagimoto, H., Toyama, H., Kodama, Y., Fukumoto, T."Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma". Oncology Letters 30.4 (2025): 466.
Chicago
Ishihara, N., Komatsu, S., Yano, Y., Fujishima, Y., Ishida, J., Kido, M., Gon, H., Fukushima, K., Urade, T., Yanagimoto, H., Toyama, H., Kodama, Y., Fukumoto, T."Multidisciplinary strategies including local treatment to achieve drug‑free status after atezolizumab plus bevacizumab treatment in hepatocellular carcinoma". Oncology Letters 30, no. 4 (2025): 466. https://doi.org/10.3892/ol.2025.15212
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