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11

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C-reactive protein to albumin ratio predicts survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib

Tada, Toshifumi ; Kumada, Takashi ; Hiraoka, Atsushi ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Scientific Reports Vol. 12, No. 1 ( 2022-05-19)

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In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-05-19)

Abstract: We investigated the impact of C-reactive protein to albumin ratio (CAR) on predicting outcomes in 522 patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib. We determined the optimal CAR cutoff value with time-dependent receiver operating characteristic curve analysis. Additionally, we clarified the relationship between CAR and liver function or HCC progression. Median overall survival was 20.0 (95% confidence interval (CI), 17.2–22.6) months. The optimal CAR cutoff value was determined to be 0.108. Multivariate analysis showed that high CAR (≥ 0.108) (hazard ratio (HR), 1.915; 95% CI, 1.495–2.452), Eastern Cooperative Oncology Group performance status ≥ 1 (HR, 1.429), and α-fetoprotein ≥ 400 ng/mL (HR, 1.604) were independently associated with overall survival. Cumulative overall survival differed significantly between patients with low versus high CAR ( p 〈 0.001). Median progression-free survival was 7.5 (95% CI, 6.7–8.1) months. Multivariate analysis showed that age, CAR ≥ 0.108 (HR, 1.644; 95% CI, 1.324–2.043), and non-hepatitis B, non-hepatitis C etiology (HR, 0.726) were independently associated with progression-free survival. Cumulative progression-free survival differed significantly between patients with low versus high CAR ( p 〈 0.001). CAR values were significantly higher as Japan Integrated Staging score increased ( p 〈 0.001). In conclusion, CAR can predict outcomes in patients with unresectable HCC treated with lenvatinib.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-022-12058-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2615211-3

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12

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Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?

Rimini, Margherita ; Persano, Mara ; Tada, Toshifumi ; [et al.]

Springer Science and Business Media LLC ; 2023

In: Targeted Oncology Vol. 18, No. 2 ( 2023-03), p. 221-233

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In: Targeted Oncology, Springer Science and Business Media LLC, Vol. 18, No. 2 ( 2023-03), p. 221-233

Type of Medium: Online Resource

ISSN: 1776-2596 , 1776-260X

URL: Article

DOI: 10.1007/s11523-023-00953-x

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2222136-0

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13

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Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population

Casadei-Gardini, Andrea ; Rimini, Margherita ; Tada, Toshifumi ; [et al.]

Elsevier BV ; 2023

In: European Journal of Cancer Vol. 180 ( 2023-02), p. 9-20

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In: European Journal of Cancer, Elsevier BV, Vol. 180 ( 2023-02), p. 9-20

Type of Medium: Online Resource

ISSN: 0959-8049

URL: Article

DOI: 10.1016/j.ejca.2022.11.017

RVK:

XA 42017.A

RVK:

XA 42017

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 1120460-6

detail.hit.zdb_id: 1468190-0

detail.hit.zdb_id: 82061-1

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14

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Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Persano, Mara ; Rimini, Margherita ; Tada, Toshifumi ; [et al.]

Elsevier BV ; 2023

In: European Journal of Cancer Vol. 189 ( 2023-08), p. 112933-

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In: European Journal of Cancer, Elsevier BV, Vol. 189 ( 2023-08), p. 112933-

Type of Medium: Online Resource

ISSN: 0959-8049

URL: Article

DOI: 10.1016/j.ejca.2023.05.021

RVK:

XA 42017.A

RVK:

XA 42017

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 1120460-6

detail.hit.zdb_id: 1468190-0

detail.hit.zdb_id: 82061-1

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15

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Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study

Tanaka, Kazunari ; Tsuji, Kunihiko ; Hiraoka, Atsushi ; [et al.]

MDPI AG ; 2023

In: Cancers Vol. 15, No. 17 ( 2023-08-31), p. 4348-

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In: Cancers, MDPI AG, Vol. 15, No. 17 ( 2023-08-31), p. 4348-

Abstract: Aim: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. Materials/Methods: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin–bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. Results: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p 〈 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6–21.3), 7.7 months (95% CI 5.3–8.9), and 5.8 months (95% CI 3.0–7.6), respectively (p 〈 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. Conclusions: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.

Type of Medium: Online Resource

ISSN: 2072-6694

URL: Article

DOI: 10.3390/cancers15174348

Language: English

Publisher: MDPI AG

Publication Date: 2023

detail.hit.zdb_id: 2527080-1

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16

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α‐FAtE : A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Rossari, Federico ; Tada, Toshifumi ; Suda, Goki ; [et al.]

Wiley ; 2024

In: International Journal of Cancer Vol. 154, No. 6 ( 2024-03-15), p. 1043-1056

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In: International Journal of Cancer, Wiley, Vol. 154, No. 6 ( 2024-03-15), p. 1043-1056

Abstract: Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first‐line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real‐world AB‐treated HCC patients were analyzed in uni‐ and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α‐FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni‐ and multivariate analyses for OS of a comparable lenvatinib‐treated HCC population. Finally, comparison between treatments was performed in patients with low and high α‐FAtE scores and predictivity estimated by interaction analysis. Time‐to‐progression (TTP) was a secondary endpoint. OS of AB‐treated HCC patients was statistically longer in those with α‐fetoprotein 〈 400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) 〈 125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α‐FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p 〈 .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p 〈 .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α‐FAtE score resulted as negative predictive factor of response to AB ( p = .0004). In conclusion, α‐FAtE is a novel prognostic and predictive score of response to first‐line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB.

Type of Medium: Online Resource

ISSN: 0020-7136 , 1097-0215

URL: Issue

URL: Article

DOI: 10.1002/ijc.v154.6

DOI: 10.1002/ijc.34799

RVK:

XA 10000

Language: English

Publisher: Wiley

Publication Date: 2024

detail.hit.zdb_id: 218257-9

detail.hit.zdb_id: 1474822-8

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17

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Early Relative Change in Hepatic Function with Lenvatinib for Unresectable Hepatocellular Carcinoma

Hiraoka, Atsushi ; Kumada, Takashi ; Atsukawa, Masanori ; [et al.]

S. Karger AG ; 2019

In: Oncology Vol. 97, No. 6 ( 2019), p. 334-340

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In: Oncology, S. Karger AG, Vol. 97, No. 6 ( 2019), p. 334-340

Abstract: 〈 b 〉 〈 i 〉 Background/Aim: 〈 /i 〉 〈 /b 〉 Lenvatinib (LEN) has been developed for the treatment of unresectable hepatocellular carcinoma (u-HCC). We aimed to elucidate the relative change in hepatic reserve function early following LEN treatment in affected patients. 〈 b 〉 〈 i 〉 Materials/Methods: 〈 /i 〉 〈 /b 〉 From March 2018 to April 2019, 123 u-HCC patients (median age 71 years; male:female ratio 95:28; Child-Pugh score 5:6:7 = 65:50:8; modified albumin-bilirubin [mALBI] grade 1:2a:2b:3 = 44:28:50:1, Barcelona Clinic Liver Cancer stage A:B:C = 1:49:73) were enrolled. Relative changes in hepatic reserve function at 2 and 4 weeks after starting LEN were retrospectively evaluated. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The median survival was 11.3 months. The Child-Pugh score declined from the start to 4 weeks after commencing LEN (score 5:6:7:8:9:≥10 = 65:50:8:0:0:0 vs. 50:39:22:8:0:4, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001). A comparison among ALBI scores at the start of LEN and those at 2 and 4 weeks revealed significant relative changes (–2.36 ± 0.45 to –2.20 ± 0.49 at 2 weeks, –2.15 ± 0.50 at 4 weeks, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001, Bonferroni method), while there was no significant difference between those at 2 and 4 weeks ( 〈 i 〉 p 〈 /i 〉 = 0.210, Bonferroni method). Assessments of relative changes of ALBI score in patients divided by mALBI grade 1, 2a, and 2b or more showed a significant decline in score regardless of grade (–2.82 ± 0.17 to –2.53 ± 0.34, 〈 i 〉 p 〈 /i 〉 & #x3c; 0.001; –2.46 ± 0.10 to –2.31 ± 0.33, 〈 i 〉 p 〈 /i 〉 = 0.017; and –1.90 ± 0.26 to –1.75 ± 0.42, 〈 i 〉 p 〈 /i 〉 = 0.009, respectively). 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Decline in hepatic function is common in the early stage (≤4 weeks, especially within 2 weeks) after introducing LEN. It is important to introduce molecular targeting agent drugs for u-HCC in patients with better hepatic function, who show transarterial catheter chemoembolization failure, as much as possible, along with consideration of the negative influence of LEN on the early response of hepatic function.

Type of Medium: Online Resource

ISSN: 0030-2414 , 1423-0232

URL: Article

DOI: 10.1159/000502095

RVK:

XH 3305

Language: English

Publisher: S. Karger AG

Publication Date: 2019

detail.hit.zdb_id: 1483096-6

detail.hit.zdb_id: 250101-6

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18

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Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real‐world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial

Tada, Toshifumi ; Kumada, Takashi ; Hiraoka, Atsushi ; [et al.]

Wiley ; 2024

In: Alimentary Pharmacology & Therapeutics Vol. 60, No. 2 ( 2024-07), p. 233-245

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In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 60, No. 2 ( 2024-07), p. 233-245

Abstract: Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC). Aims To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real‐world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial. Methods A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non‐IMbrave150 group). Results Median progression‐free survival (PFS) in the IMbrave150 and non‐IMbrave150 groups was 7.4 months and 5.6 months ( p = 0.002). Multivariable analysis revealed that non‐B, non‐C HCC aetiology (hazard ratio [HR], 1.173), α‐fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin–bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non‐Imbrave150 groups was 26.5 and 18.8 months ( p 〈 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α‐fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a. Conclusions Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.

Type of Medium: Online Resource

ISSN: 0269-2813 , 1365-2036

URL: Issue

URL: Article

DOI: 10.1111/apt.v60.2

DOI: 10.1111/apt.18037

Language: English

Publisher: Wiley

Publication Date: 2024

detail.hit.zdb_id: 2003094-0

SSG: 15,3

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19

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Correction to: Development and validation of a modified albumin–bilirubin grade and α-fetoprotein score (mALF score) for hepatocellular carcinoma patients receiving atezolizumab and bevacizumab

Hatanaka, Takeshi ; Kakizaki, Satoru ; Hiraoka, Atsushi ; [et al.]

Springer Science and Business Media LLC ; 2023

In: Hepatology International Vol. 17, No. 1 ( 2023-02), p. 271-273

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In: Hepatology International, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2023-02), p. 271-273

Type of Medium: Online Resource

ISSN: 1936-0533 , 1936-0541

URL: Article

DOI: 10.1007/s12072-022-10446-0

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2270316-0

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20

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Comparative efficacy and safety of atezolizumab and bevacizumab between hepatocellular carcinoma patients with viral and non‐viral infection: A Japanese multicenter observational study

Hatanaka, Takeshi ; Kakizaki, Satoru ; Hiraoka, Atsushi ; [et al.]

Wiley ; 2023

In: Cancer Medicine Vol. 12, No. 5 ( 2023-03), p. 5293-5303

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In: Cancer Medicine, Wiley, Vol. 12, No. 5 ( 2023-03), p. 5293-5303

Abstract: This study compared the efficacy and safety of atezolizumab and bevacizumab (Atez/Bev) in patients with viral and non‐viral infection in clinical settings. Methods We conducted the retrospective cohort study of 323 BCLC stage B or C hepatocellular carcinoma (HCC) patients with Child‐Pugh class A, and a performance status of 0 or 1 who started Atez/Bev from September 2020 to December 2021 at 22 institutions in Japan. Patients with viral infection was defined as those who were either serum anti‐HCV‐ Ab or HBs‐Ag‐positive, while patients with non‐viral infection was defined as those who were both serum anti‐HCV Ab‐ and HBs‐Ag‐negative. We constructed a propensity‐score‐matched cohort to minimize the risk of observable potential confounders. Results Propensity score matching produced 126 matched pairs for patients with viral versus non‐viral infection. After matching, the significant differences in baseline demographic features did not exist between the two groups. The objective response rate was 20.6% and 24.6% in viral‐ and non‐viral‐related HCC patients, respectively, without a significant difference ( p = 0.55). The disease control rate was not also significantly different (68.3% vs 69.0%, p = 1.00). The median progression‐free survival was 7.0 months (95% confidence interval [CI] 6.0–9.6) and 6.2 months (95% CI 5.1–7.8) in patients with viral and non‐viral infection, and the 12‐month survival rates were 65.5% (95% CI 50.8–76.8) and 71.7% (95% CI 57.3–81.9) in those with viral and non‐viral infection, respectively, which were not significantly different ( p = 0.33, p = 0.38). No significant difference in treatment‐related adverse events was found between the two groups. Conclusions Our etiology‐based study demonstrated that Atez/Bev showed good efficacy and safety for HCC patient with non‐viral infection as well as those with viral infection.

Type of Medium: Online Resource

ISSN: 2045-7634 , 2045-7634

URL: Issue

URL: Article

DOI: 10.1002/cam4.v12.5

DOI: 10.1002/cam4.5337

Language: English

Publisher: Wiley

Publication Date: 2023

detail.hit.zdb_id: 2659751-2

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