Prediction of Therapeutic Response Using Contrast-Enhanced Ultrasound in Japanese Patients Treated with Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma

Takada H. · Yamashita K. · Osawa L. · Komiyama Y. · Nakakuki N. · Muraoka M. · Suzuki Y. · Sato M. · Takano S. · Fukasawa M. · Yamaguchi T. · Maekawa S. · Enomoto N.

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Gastroenterology and Hepatology Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

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Article / Publication Details

First-Page Preview

Abstract of Clinical Study

Received: August 04, 2022
Accepted: October 17, 2022
Published online: December 14, 2022

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 5

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

Abstract

Introduction: Atezolizumab and bevacizumab (AB) therapy was the first-line treatment for unresectable hepatocellular carcinoma (u-HCC). However, the predictive marker of therapeutic response that can be easily used in clinical practice is still unknown. We prospectively investigated the utility of time-intensity curve (TIC) analysis using contrast-enhanced ultrasound (CEUS) as a predictive indicator of therapeutic response after the start of AB therapy. Methods: Thirty-five patients who received AB therapy for u-HCC were included in this study. TIC analysis was performed in 28 patients who were able to undergo CEUS before and 3–7 days after administration. We analyzed prognostic factors related to the initial therapeutic response and long progression-free survival (PFS). Results: The initial therapeutic response using dynamic computed tomography or Gd-EOB magnetic resonance imaging at 8–12 weeks after administration was partial response/stable disease/progressive disease (PD) in 14/12/9 cases (40/34/26%). Cases with PD (n = 9) had more cases without decreased blood flow in TIC analysis compared with cases with non-PD (100 vs. 18%, p = 0.001). Cases without decreased blood flow in TIC analysis (n = 10) had more cases with PD compared with cases with decreased blood flow (60 vs. 0%, p = 0.001). PFS in patients without decreased blood flow early after the administration was shorter than that in those with decreased blood flow (9.1 vs. 28 weeks, p = 0.0051). Conclusion: Early evaluation by TIC analysis using CEUS may be useful in predicting the therapeutic response in patients treated with AB therapy for u-HCC.

© 2022 S. Karger AG, Basel

References Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–905. Cheng AL, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Updated efficacy and safety data from IMbrave150: atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J Hepatol. 2022;76(4):862–73. Galle PR, Finn RS, Qin S, Ikeda M, Zhu AX, Kim TY, et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(7):991–1001. Gordan JD, Kennedy EB, Abou-Alfa GK, Beg MS, Brower ST, Gade TP, et al. Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline. J Clin Oncol. 2020;38(36):4317–45. Llovet JM, Villanueva A, Marrero JA, Schwartz M, Meyer T, Galle PR, et al. Trial design and endpoints in hepatocellular carcinoma: AASLD consensus conference. Hepatology. 2021;73(Suppl 1):158–91. Kudo M, Han KH, Ye SL, Zhou J, Huang YH, Lin SM, et al. A changing paradigm for the treatment of intermediate-stage hepatocellular carcinoma: asia-pacific primary liver cancer expert consensus statements. Liver Cancer. 2020;9(3):245–60. Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, et al. Safety and efficacy of atezolizumab plus bevacizumab in elderly patients with hepatocellular carcinoma: a multicenter analysis. Cancer Med. 2022;11(20):3796–808. Hiraoka A, Kumada T, Tada T, Hirooka M, Kariyama K, Tani J, et al. Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma: early clinical experience. Cancer Rep. 2022;5(2):e1464. Hayakawa Y, Tsuchiya K, Kurosaki M, Yasui Y, Kaneko S, Tanaka Y, et al. Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice. Invest New Drugs. 2022;40(2):392–402. Hatanaka T, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, et al. Association of early bevacizumab interruption with efficacy of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma: a landmark analysis. Hepatol Res. 2022;52(5):462–70. Siegel AB, Cohen EI, Ocean A, Lehrer D, Goldenberg A, Knox JJ, et al. Phase II trial evaluating the clinical and biologic effects of bevacizumab in unresectable hepatocellular carcinoma. J Clin Oncol. 2008;26(18):2992–8. Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics. Semin Cancer Biol. 2018;52(Pt 2):117–24. Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP, et al. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol. 1998;160(3):1224–32. Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D, et al. Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 2011;91(3):1071–121. Motz GT, Santoro SP, Wang LP, Garrabrant T, Lastra RR, Hagemann IS, et al. Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med. 2014;20(6):607–15. Shiozawa K, Watanabe M, Kikuchi Y, Kudo T, Maruyama K, Sumino Y. Evaluation of sorafenib for hepatocellular carcinoma by contrast-enhanced ultrasonography: a pilot study. World J Gastroenterol. 2012;18(40):5753–8. Sugimoto K, Moriyasu F, Saito K, Rognin N, Kamiyama N, Furuichi Y, et al. Hepatocellular carcinoma treated with sorafenib: early detection of treatment response and major adverse events by contrast-enhanced US. Liver Int. 2013;33(4):605–15. Yoshida K, Hirokawa T, Moriyasu F, Liu L, Liu GJ, Yamada M, et al. Arterial-phase contrast-enhanced ultrasonography for evaluating anti-angiogenesis treatment: a pilot study. World J Gastroenterol. 2011;17(8):1045–50. Lavisse S, Lejeune P, Rouffiac V, Elie N, Bribes E, Demers B, et al. Early quantitative evaluation of a tumor vasculature disruptive agent AVE8062 using dynamic contrast-enhanced ultrasonography. Invest Radiol. 2008;43(2):100–11. Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30(1):52–60. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8. Kuzuya T, Kawabe N, Hashimoto S, Miyahara R, Nakano T, Nakaoka K, et al. Initial experience of atezolizumab plus bevacizumab for advanced hepatocellular carcinoma in clinical practice. Cancer Diagn Progn. 2021;1(2):83–8. Iwamoto H, Shimose S, Noda Y, Shirono T, Niizeki T, Nakano M, et al. Initial experience of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in real-world clinical practice. Cancers. 2021;13(11):2786. Chuma M, Uojima H, Hattori N, Arase Y, Fukushima T, Hirose S, et al. Safety and efficacy of atezolizumab plus bevacizumab in patients with unresectable hepatocellular carcinoma in early clinical practice: a multicenter analysis. Hepatol Res. 2022;52(3):269–80. Lassau N, Koscielny S, Albiges L, Chami L, Benatsou B, Chebil M, et al. Metastatic renal cell carcinoma treated with sunitinib: early evaluation of treatment response using dynamic contrast-enhanced ultrasonography. Clin Cancer Res. 2010;16(4):1216–25. Lassau N, Lamuraglia M, Chami L, Leclère J, Bonvalot S, Terrier P, et al. Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography. AJR Am J Roentgenol. 2006;187(5):1267–73. Lassau N, Chami L, Koscielny S, Chebil M, Massard C, Benatsou B, et al. Quantitative functional imaging by dynamic contrast enhanced ultrasonography (DCE-US) in GIST patients treated with masatinib. Invest New Drugs. 2012;30(2):765–71. Matsumoto N, Ogawa M, Kaneko M, Arima S, Kumagawa M, Watanabe Y, et al. Contrast-enhanced ultrasonography for blood flow detection in hepatocellular carcinoma during lenvatinib therapy. J Med Ultrason. 2022;49(3):425–32. Kuorda H, Abe T, Fujiwara Y, Okamoto T, Yonezawa M, Sato H, et al. Change in arterial tumor perfusion is an early biomarker of lenvatinib efficacy in patients with unresectable hepatocellular carcinoma. World J Gastroenterol. 2019;25(19):2365–72. Kamachi N, Nakano M, Okamura S, Niizeki T, Iwamoto H, Shimose S, et al. Evaluating the therapeutic effect of lenvatinib against advanced hepatocellular carcinoma by measuring blood flow changes using contrast-enhanced ultrasound. Cancer Rep. 2022;5(2):e1471. Zhu AX, Holalkere NS, Muzikansky A, Horgan K, Sahani DV. Early antiangiogenic activity of bevacizumab evaluated by computed tomography perfusion scan in patients with advanced hepatocellular carcinoma. Oncologist. 2008;13(2):120–5. Ren Y, Fleischmann D, Foygel K, Molvin L, Lutz AM, Koong AC, et al. Antiangiogenic and radiation therapy: early effects on in vivo computed tomography perfusion parameters in human colon cancer xenografts in mice. Invest Radiol. 2012;47(1):25–32. Anzidei M, Napoli A, Zaccagna F, Cartocci G, Saba L, Menichini G, et al. Liver metastases from colorectal cancer treated with conventional and antiangiogenetic chemotherapy: evaluation with liver computed tomography perfusion and magnetic resonance diffusion-weighted imaging. J Comput Assist Tomogr. 2011;35(6):690–6. Scheiner B, Pomej K, Kirstein MM, Hucke F, Finkelmeier F, Waidmann O, et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy: development and validation of the CRAFITY score. J Hepatol. 2022;76(2):353–63. Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T, et al. Initial experience of ramucirumab treatment after lenvatinib failure for patients with advanced hepatocellular carcinoma. Anticancer Res. 2020;40(4):2089–93. Lee PC, Chao Y, Chen MH, Lan KH, Lee CJ, Lee IC, et al. Predictors of response and survival in immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma. Cancers. 2020;12(1):182. Shao YY, Liu TH, Hsu C, Lu LC, Shen YC, Lin ZZ, et al. Early alpha-foetoprotein response associated with treatment efficacy of immune checkpoint inhibitors for advanced hepatocellular carcinoma. Liver Int. 2019;39(11):2184–9. Kuzuya T, Kawabe N, Hashimoto S, Miyahara R, Sawaki A, Nakano T, et al. Early changes in alpha-fetoprotein are a useful predictor of efficacy of atezolizumab plus bevacizumab treatment in patients with advanced hepatocellular carcinoma. Oncology. 2022;100(1):12–21. Article / Publication Details

First-Page Preview

Abstract of Clinical Study

Received: August 04, 2022
Accepted: October 17, 2022
Published online: December 14, 2022

Number of Print Pages: 12
Number of Figures: 5
Number of Tables: 5

ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)

For additional information: https://www.karger.com/OCL

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