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. 2025 Aug;55(8):1184-1192.
doi: 10.1111/hepr.14212. Epub 2025 May 28.

A novel approach to evaluate the therapeutic efficacy of durvalumab and tremelimumab combination therapy in hepatocellular carcinoma

Tetsu Tomonari  1   2 , Shigeo Shimose  3 , Issei Saeki  4 , Joji Tani  5 , Yuichi Honma  6 , Takanori Ito  7 , Mamiko Takeuchi  8 , Takehito Naito  9 , Yasuto Takeuchi  10 , Ryu Sasaki  11 , Kyo Sasaki  12 , Takeshi Hatanaka  13 , Satoru Kakizaki  14 , Yuki Kanayama  13 , Atsushi Naganuma  14 , Norikazu Tanabe  4 , Hironori Tanaka  1 , Yutaka Kawano  1 , Yasushi Sato  1 , Sohji Nishina  12 , Hisamitsu Miyaaki  11 , Motoyuki Otsuka  10 , Hiroki Kawashima  7 , Masaru Harada  6 , Hideki Kobara  5 , Taro Takami  4 , Takumi Kawaguchi  3 , Tetsuji Takayama  1 ; Hepatology InVestigator Experts in Japan (HIVE‐J) Study Group
Affiliations

A novel approach to evaluate the therapeutic efficacy of durvalumab and tremelimumab combination therapy in hepatocellular carcinoma

Tetsu Tomonari et al. Hepatol Res. 2025 Aug.

Abstract

Aim: This study aimed to evaluate the efficacy of durvalumab + tremelimumab (Dur + Tre) in real-world clinical practice, characterize "stable disease (SD)," and identify SD responders (SD-R) who benefit from Dur + Tre treatment.

Methods: This multicenter observational study included 212 patients with unresectable hepatocellular carcinoma (u-HCC) treated with Dur + Tre between March 2023 and November 2024. The patients were categorized into 95 first-line and 117 later-line cases, respectively. Sequential cutoff points for depth of response (DOR) and progression-free survival (PFS) were tested to identify subgroups with survival outcomes comparable to those of responders.

Results: Disease control rate (DCR) and PFS were significantly better in the first-line setting for both response evaluation criteria in solid tumors (RECIST) and modified RECIST (mRECIST) criteria. Patients who achieved PFS of ≥84 days or RECIST DOR of ≤-10% were classified as SD-R, as they had long-term survival outcomes similar to those with PR or CR. Furthermore, the CR + PR + SD-R group had significantly better survival outcomes than the other groups (p < 0.01), and multivariate analysis confirmed that SD-R was an independent prognostic factor with the strongest impact on survival outcomes (hazard ratio = 0.11).

Conclusions: In real-world clinical practice, Dur + Tre is highly effective as a first-line treatment for u-HCC. Additionally, patients with SD who met the SD-R criteria (PFS ≥84 days or RECIST DOR ≤-10%) showed survival outcomes comparable to those of patients with PR or CR. These findings may help identify patients who are most likely to benefit from treatment and improve their prognoses.

Keywords: durvalumab plus tremelimumab; hepatocellular carcinoma; immune checkpoint inhibitors.

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References

REFERENCES

    1. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet. 2018;391(10127):1301–1314. https://doi.org/10.1016/s0140‐6736(18)30010‐2
    1. Nault JC, Galle PR, Marquardt JU. The role of molecular enrichment on future therapies in hepatocellular carcinoma. J Hepatol. 2018;69(1):237–247. https://doi.org/10.1016/j.jhep.2018.02.016
    1. 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):1894–1905. https://doi.org/10.1056/nejmoa1915745
    1. Sangro B, Chan SL, Kelley RK, Lau G, Kudo M, Sukeepaisarnjaroen W, et al. Four‐year overall survival update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Ann Oncol. 2024;35(5):448–457. https://doi.org/10.1016/j.annonc.2024.02.005
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–247. https://doi.org/10.1016/j.ejca.2008.10.026

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