Early Prediction of Response Focused on Tumor Markers in Atezolizumab plus Bevacizumab Therapy for Hepatocellular Carcinoma

Tanabe, Norikazu; Saeki, Issei; Aibe, Yuki; Matsuda, Takashi; Hanazono, Tadasuke; Nishi, Maiko; Hidaka, Isao; Kuwashiro, Shinya; Shiratsuki, Shogo; Matsuura, Keiji; Egusa, Maho; Nishiyama, Natsuko; Fujioka, Tsuyoshi; Kawamoto, Daiki; Sasaki, Ryo; Nishimura, T.; Oono, Takashi; Hisanaga, Takuro; Matsumoto, Toshihiko; Ishikawa, Tsuyoshi; Yamasaki, Takahiro; Takami, Taro

doi:10.3390/cancers15112927

Cited by 7 publications

(2 citation statements)

References 33 publications

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“…However, it has been reported that patients who achieved DCR during Dur/Tre treatment had longer median survival ( 20 ). Thus, achieving DCR during immunotherapy is important for longer survival ( 21 ). Although there was no significant difference in PFS between the first-line and later-line therapies in this study, this result may change if the observation period is extended.…”

Section: Discussionmentioning

confidence: 99%

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice

Shimose,

Saeki,

Tomonari

et al. 2024

Oncol Lett

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Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age.

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Section: Discussionmentioning

confidence: 99%

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice

Shimose,

Saeki,

Tomonari

et al. 2024

Oncol Lett

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“…However, AFP has limited value, as only a minority of patients have increased levels (10% of patients at early stages have AFP >400 ng/dL scaling up to 40% in advanced stages) [ 10 , 11 ]. On the other hand, early changes in AFP may predict the benefit of systemic agents like Ramucirumab [ 9 ] or the combination of Atezolizumab plus Bevacizumab [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment

Sogbe,

Bilbao,

Marchese

et al. 2024

Clin Mol Hepatol

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Background/Aims: New prognostic markers are needed to identify patients with hepatocellular carcinoma (HCC) who carry a worse prognosis. Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess both circulating tumor DNA (ctDNA) fraction and large structural genomic alterations. Here, we studied the performance of ULP-WGS of plasma cfDNA to infer prognosis in patients with HCC.Methods: Plasma samples were obtained from patients with HCC prior to surgery, locoregional or systemic therapy, and were analyzed by ULP-WGS of cfDNA to an average genome-wide fold coverage of 0.3x. ctDNA and copy number alterations (CNA) were estimated using the software package ichorCNA.Results: Samples were obtained from 73 HCC patients at different BCLC stages (BCLC 0/A: n=37, 50.7%; BCLC B/C: n=36, 49.3%). ctDNA was detected in 18 out of 31 patients who received systemic treatment. Patients with detectable ctDNA showed significantly worse overall survival (median, 13.96 months vs not reached). ctDNA remained an independent predictor of prognosis after adjustment by clinical-pathologic features and type of systemic treatment (hazard ratio 7.69; 95%, CI 2.09–28.27). Among ctDNA-positive patients under systemic treatments, the loss of large genomic regions in 5q and 16q arms was associated with worse prognosis after multivariate analysis.Conclusions: ULP-WGS of cfDNA provides clinically relevant information about the tumor biology. The presence of ctDNA and the loss of 5q and 16q arms in ctDNA-positive patients are independent predictors of worse prognosis in patients with advanced HCC receiving systemic therapy.

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Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma

Miura,

Ono,

Nakahara

et al. 2024

J Gastroenterol

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Background This study aims to identify biomarkers for treatment response of atezolizumab plus bevacizumab (Atezo+Bev) in patients with hepatocellular carcinoma (HCC). Methods 96 patients who received Atezo+Bev or lenvatinib as a first-line systemic therapy were enrolled as the training group after propensity score matching (PSM), and 42 patients treated with Atezo+Bev were enrolled as the validation group. 17 serum cytokines were measured by Luminex multiplex assay at the start of treatment. For further assessment of the association between cytokine levels and the tumor microenvironment (TME), immunohistochemistry (IHC) was performed on pre-treatment liver biopsy specimens. Results In the derivation set, multivariate analysis identified elevated IL-6 as an independent risk factor in the Atezo+Bev group (HR 5.80: p<0.01), but not in the lenvatinib group; in a subset analysis of patients with low IL-6, PFS was longer in the Atezo+Bev training group than in the lenvatinib group (p = 0.02). A validation study also showed a significantly longer prognosis in the low IL-6 group for both PFS (p = 0.0001) and OS (p = 0.03). Serum IL-6 had a positive correlation with tumor IL-6 expression (ρ = 0.56, p < 0.0001) and an inverse correlation with the CD8/CD163-positive cell count ratio (ρ = −0.4, p < 0.01). Conclusion Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.

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Early Prediction of Response Focused on Tumor Markers in Atezolizumab plus Bevacizumab Therapy for Hepatocellular Carcinoma

Cited by 7 publications

References 33 publications

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice

Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real‑world practice

Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment

Serum IL-6 concentration is a useful biomarker to predict the efficacy of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma

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