Disease Etiology and Outcomes After Atezolizumab Plus Bevacizumab in Hepatocellular Carcinoma: Post-Hoc Analysis of IMbrave150

Espinoza, Magdalena; Muiquith, Maishara; Lim, Mir; Zhu, Hai‐Liang; Singal, Amit G.; Hsiehchen, David

doi:10.1053/j.gastro.2023.02.042

Cited by 34 publications

(18 citation statements)

References 9 publications

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“… 19 In contrast, we observed no relevant influence on the PFS in patients treated with Atez/Bev across different etiologies, but the shortest PFS was observed in patients with hepatitis B, aligning with the latest published posthoc analysis of IMbrave150 study. 23 Nevertheless, the study shows a disease control rate of 72.8% for patients with hepatitis B. In our cohort of patients, we observed high efficacy of Atez/Bev especially for non-viral HCC such as NASH, as we recorded the longest PFS compared to the other treatments.…”

Section: Discussionmentioning

confidence: 59%

First-Line Treatment for Advanced Hepatocellular Carcinoma: A Three-Armed Real-World Comparison

Mahn,

Glüer,

Sadeghlar

et al. 2024

JHC

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Background and Aim There are several existing systemic 1st- line therapies for advanced hepatocellular carcinoma (HCC), including atezolizumab/bevacizumab (Atez/Bev), sorafenib and lenvatinib. This study aims to compare the effectiveness of these three 1st-line systemic treatments in a real-world setting for HCC, focusing on specific patient subgroups analysis. Methods A total of 177 patients with advanced HCC treated with Atez/Bev (n = 38), lenvatinib (n = 21) or sorafenib (n = 118) as 1st line systemic therapy were retrospectively analyzed and compared. Primary endpoints included objective response rate (ORR), progression-free survival (PFS) and 15-month overall survival (15-mo OS). Subgroups regarding liver function, etiology, previous therapy and toxicity were analyzed. Results Atez/Bev demonstrated significantly longer median 15-month OS with 15.03 months compared to sorafenib with 9.43 months (p = 0.04) and lenvatinib with 8.93 months (p = 0.05). Similarly, it had highest ORR of 31.6% and longest median PFS with 7.97 months, independent of etiology. However, significantly superiority was observed only compared to sorafenib (ORR: 4.2% (p < 0.001); PFS: 4.57 months (p = 0.03)), but not comparing to lenvatinib (ORR: 28.6% (p = 0.87); PFS: 3.77 months (p = 0.10)). Atez/Bev also resulted in the longest PFS in patients with Child-Pugh A and ALBI 1 score and interestingly in those previously treated with SIRT. Contrary, sorafenib was non inferior in patients with impaired liver function. Conclusion Atez/Bev achieved longest median PFS and 15-mo OS independent of etiology and particularly in patients with stable liver function or prior SIRT treatment. Regarding therapy response lenvatinib was non-inferior to Atez/Bev. Finally, sorafenib seemed to perform best for patients with deteriorated liver function.

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Section: Discussionmentioning

confidence: 59%

First-Line Treatment for Advanced Hepatocellular Carcinoma: A Three-Armed Real-World Comparison

Mahn,

Glüer,

Sadeghlar

et al. 2024

JHC

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“…In a meta‐analysis involving six randomised controlled trials using ICIs, a significant survival benefit was evident across both non‐viral and viral aetiologies (HR = .79, 95% CI [.72 to .86], p < .001), with the most notable advantage observed in patients with hepatitis B (hepatitis B: HR = .70, p < .001; hepatitis C: HR = .78, p = .04; non‐viral: HR = .87, p = .02). The recent Post‐Hoc analysis of Imbrave150 did not observe differences in PFS and OS according to the aetiology 15 . Thus, the postulated reduced activity of immunotherapy in non‐viral‐related HCC was mostly based on a mouse model and clinical evidence remains not robust.…”

Section: Discussionmentioning

confidence: 98%

“…As liver function was associated with PFS, the same types of analysis were performed restricted to Child-Pugh A patients with cirrhosis. 16 [10][11][12][13][14][15][16][17][18][19][20][21][22][23] 15 [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] 15 [11][12][13][14][15][16][17][18][19][20][21][22][23] 12 [8][9][10][11][12][13][14][15][16] 15…”

Section: The Presence Of Masld Was Not Associated With Pfsmentioning

confidence: 99%

“…1,14 The study successfully met its endpoint, demonstrating a superior OS differences in PFS and OS according to the aetiology. 15 Thus, the postulated reduced activity of immunotherapy in non-viral-related HCC was mostly based on a mouse model and clinical evidence remains not robust. Indeed, the data still do not decisively demonstrate that patients with non-viral liver disease do not benefit from ICI-based therapy, and the entity 'non-viral' needs to be defined, emphasising the necessity for further comprehensive investigations.…”

Section: No Impact Of Mrf or Masld On The Occurrence Of Immune-relate...mentioning

confidence: 99%

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No correlation between MASLD and poor outcome of Atezolizumab‐Bevacizumab therapy in patients with advanced HCC

Copil,

Campani,

Lequoy

et al. 2024

Liver International

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IntroductionIt has been suggested that in patients with hepatocellular carcinoma (HCC) of metabolic aetiology, the efficacy of immunotherapy may be reduced. The aim was to investigate the impact of metabolic‐associated steatotic liver disease (MASLD) and metabolic risk factors (MRF) on the outcomes of Atezolizumab‐Bevacizumab (AtezoBev).MethodsWe collected data from 295 AtezoBev‐treated patients, starting in 2020. MASLD was defined by the current/past presence of MRF, namely BMI ≥ 30 kg/m2, type 2 diabetes, arterial hypertension or dyslipidaemia and no other cause of liver disease (daily alcohol ≤30 g in males and ≤20 g in females). The influence of baseline characteristics on progression (PFS) and overall survival (OS) was assessed by uni/multivariate analysis using the Cox model.ResultsRisk factors for cirrhosis were viral infection in 47%, excessive alcohol consumption in 45% and MASLD in 13%. In the whole cohort, 27% had 1 MRF, 23% had 2 MRF, 15% had 3 MRF and 6% had 4 MRF. Median PFS and OS were 6.5 and 15.6 months, respectively, and similar in patients with or without MASLD in Log rank analysis. The number of MRF or MALSD was not associated with PFS or OS in the univariate analysis. Factors associated with PFS in multivariate analysis included ALBI grade 3 (HR = 1.60, p = .03), AFP (HR = 1.01, p = .01) and metastasis (HR = 1.77, p < .001). During follow‐up, 10% of patients experienced immune‐related adverse events, with age and female gender, but not MRF or MASLD, as independent predictors.ConclusionOur study suggests that the presence of MASLD or the number of MRF did not lead to worse outcomes in advanced HCC patients treated with AtezoBev.

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“…Although some evidence has indicated a lower benefit of immunotherapy for non-viral etiology, particularly MASH-related HCC, it has recently been shown that baseline liver disease etiology is not associated with significant differences in ORR, PFS, or OS. 47 Moreover, reporting etiology as non-viral may be misleading, as it includes heterogeneous subgroups of patients with different risk factors (alcohol-related liver disease, MAFLD/MASH, metabolic syndrome) that frequently overlap in the process of HCC development. This poorly informative classification and the lack of stratification in randomized controlled trials is still a main issue to address.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Atezolizumab and Bevacizumab Combination as a First Line Treatment of Advanced Hepatocellular Carcinoma

Zanuso,

Pirozzi,

Balsano

et al. 2023

JHC

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Hepatocellular carcinoma (HCC) is one of the most common leading causes of cancer death worldwide. As most patients are diagnosed with advanced disease, systemic therapy remains the backbone of treatment. In recent years, we have witnessed the transformation of advanced HCC treatment landscapes from single-agent targeted therapies to immunotherapy combinations, with atezolizumab plus bevacizumab becoming the new first-line standard of care with an increase in overall survival, progression-free survival, and objective response rate compared to sorafenib, and a positive impact on quality of life. Although the efficacy and safety of this combination have been confirmed regardless of ethnicity, age, and etiology, only a subgroup of patients seems to benefit the most from this treatment. Currently, predictive serum and tissue biomarkers to select patients who are most likely to respond to atezolizumab plus bevacizumab are lacking. Moreover, the optimal subsequent therapy for patients who progress on first-line atezolizumab plus bevacizumab remains unknown, clinical trials are ongoing, and real-world data are needed to determine the most effective treatment sequence. Importantly, careful evaluation of bleeding risk and preservation of adequate liver function are fundamental to improve patients’ prognosis, especially when subsequent treatments are administered.

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Disease Etiology and Outcomes After Atezolizumab Plus Bevacizumab in Hepatocellular Carcinoma: Post-Hoc Analysis of IMbrave150

Cited by 34 publications

References 9 publications

First-Line Treatment for Advanced Hepatocellular Carcinoma: A Three-Armed Real-World Comparison

First-Line Treatment for Advanced Hepatocellular Carcinoma: A Three-Armed Real-World Comparison

No correlation between MASLD and poor outcome of Atezolizumab‐Bevacizumab therapy in patients with advanced HCC

Safety and Efficacy of Atezolizumab and Bevacizumab Combination as a First Line Treatment of Advanced Hepatocellular Carcinoma

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