Atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma with impaired liver function and prior systemic therapy: a real-world experience

Huang

et al. 2023

In Vivo

Background/Aim: The combination of bevacizumab and atezolizumab (Bev-Ate) has been established as a standard first-line systemic treatment option for unresectable hepatocellular carcinoma (HCC) since 2020. This study examined the outcomes of HCC patients who received the combination in southern Taiwan. Patients and Methods: All patients were enrolled from four hospitals in Taiwan. They received Bev-Ate therapy for unresectable HCC. Results: Thirty-five patients were included; 28 (80%) had Barcelona Clinic Liver Cancer stage C disease. Hepatitis etiology was chronic hepatitis B and C in 63% and 17% of patients, respectively. Eleven (31%) patients had received prior systemic treatment for unresectable HCC. The response rate was 51%, and the disease control rate was 72% for all patients.

Section: Discussionsupporting

confidence: 88%

Bevacizumab and Atezolizumab for Unresectable Hepatocellular Carcinoma: Real-world Data in Taiwan-Tainan Medical Oncology Group H01 Trial

Huang

et al. 2023

In Vivo

“…A recent real-world study has reported that the median PFS is significantly shorter in patients who did not meet the IMbrave150 eligibility criteria than in patients who met the criteria [PFS: 3.7 months vs. 8.7 months] [ 11 ]. Although more than half of patients did not meet the eligibility criteria for IMbrave150 in this study, median PFS was similar between patients who did and those who did not meet the criteria (PFS 6.5 months (95% CI; 3.7–NE months) vs. 6.9 (95% CI; 4.2–8.9 months)).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study has revealed that OS and PFS are significantly shorter in patients with Child-Pugh B and C than in patients with Child-Pugh A [ 11 , 23 ]. In this study, the PFS and treatment response were similar between patients with Child-Pugh A and B.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported the high efficacy and safety of atezolizumab and bevacizumab for unresectable HCC in patients in the early phase of treatment who do not meet the eligibility criteria of IMbrave150 [ 10 ]. However, Tiago de Castro et al have recently reported that OS and progression-free survival (PFS) were significantly longer in patients who met the eligibility criteria of IMbrave150 than in patients who did not meet the eligibility criteria of IMbrave150 [OS: 15.0 months vs. 6.0 months; PFS: 8.7 months vs. 3.7 months, respectively] [ 11 ]. Thus, additional data for the efficacy of atezolizumab and bevacizumab in patients who do not meet IMbrave150 eligibility criteria are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150

Sho

Suda

Yamamoto

et al. 2022

Cancers

The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. −2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.

“…HCC is associated with high mortality, morbidity, and poor prognosis. Chemotherapy is the standard treatment for HCC [ 2 ], and the combination of atezolizumab and bevacizumab is the first-line treatment for advanced HCC [ 3 ]; however, the clinical safety of this combination has not yet been fully evaluated in patients [ 4 ]. Therefore, there is an urgent need to explore and discover new drugs with fewer toxic side effects to treat patients with HCC.…”

Section: Introductionmentioning

confidence: 99%

Antitumor Potential of Withanolide Glycosides from Ashwagandha (Withania somnifera) on Apoptosis of Human Hepatocellular Carcinoma Cells and Tube Formation in Human Umbilical Vein Endothelial Cells

et al. 2022

Antioxidants

Hepatocellular carcinoma (HCC) is the fastest-growing tumor capable of spreading to other organs via blood vessels formed by endothelial cells. Apoptosis and angiogenesis-targeting therapies are attractive for cancer treatment. In this study, we aimed to study the in vitro cytotoxicity of Withania somnifera against human HCC (HepG2) cells, identify potential antitumoral withanolide glycosides from the active fraction, and elucidate cytotoxic molecular mechanisms of identified bioactive compounds. W. somnifera (Solanaceae), well-known as ‘ashwagandha’, is an Ayurvedic medicinal plant used to promote health and longevity, and the MeOH extract of W. somnifera root exhibited cytotoxicity against HepG2 cells during initial screening. Bioactivity-guided fractionation of the MeOH extract and subsequent phytochemical investigation of the active n-BuOH-soluble fraction resulted in the isolation of five withanolide glycosides (1–5), including one new metabolite, withanoside XIII (1), aided by liquid chromatography–mass spectrometry-based analysis. The new compound structure was determined by 1D and 2D nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectroscopy, electronic circular dichroism, and enzymatic hydrolysis. In addition, withanoside XIIIa (1a) was identified as the new aglycone (1a) of 1. Isolated withanolide glycosides 1–5 and 1a were cytotoxic toward HepG2 cells; withagenin A diglucoside (WAD) (3) exhibited the most potent cytotoxicity against HepG2 cells, with cell viability less than 50% at 100 μM. WAD cytotoxicity was mediated by both extrinsic and intrinsic apoptosis pathways. Treatment with WAD increased protein expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, Bcl-2-associated X protein (Bax), and cleaved poly(ADP-ribose) polymerase (cleaved PARP) but decreased expression levels of B-cell lymphoma 2 (Bcl-2). Moreover, WAD inhibited tubular structure formation in human umbilical vein endothelial cells (HUVECs) by inhibiting the protein expression of vascular endothelial growth factor receptor 2 and its downstream pathways, including extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR). These effects were also enhanced by co-treatment with ERK and PI3K inhibitors. Overall, these results indicate that WAD (3) induced HepG2 apoptosis and inhibited HUVEC tube formation, suggesting its potential application in treating liver cancers.