Updated safety and clinical activity results from a phase Ib study of atezolizumab + bevacizumab in hepatocellular carcinoma (HCC)

Pishvaian, Michael J.; Lee, M.S.; Ryoo, Baek Yeol; Stein, Stacey; Lee, K.-H.; Verret, Wendy; Spahn, Jessica; Shao, Hui; Liu, B.; Iizuka, Kunio; Hsu, Chih‐Hung

doi:10.1093/annonc/mdy424.028

Cited by 68 publications

(53 citation statements)

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“…Results later were updated, still in abstract form. 41 The ORRs of 32% as per RECIST version 1.1 criteria and 34% as per modified RECIST criteria clearly appear more realistic than the initially reported ORR of 62%. Responses were observed in all clinically relevant subgroups, including patients with α-fetoprotein levels ≥400 ng/mL.…”

Section: Immunotherapy-based Combinationsmentioning

confidence: 78%

Immune checkpoint inhibitors for hepatocellular carcinoma

Dika

Khalil

Abou‐Alfa

2019

Cancer

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The position of immunotherapy as a pillar of systemic cancer treatment has been firmly established over the past decade. Immune checkpoint inhibitors are a welcome option for patients with different malignancies. This is in part because they offer the possibility of durable benefit, even for patients who have failed other treatment modalities. The recent demonstration that immunotherapy is effective for patients with hepatocellular carcinoma (HCC) is a milestone in the history of this recalcitrant disease. The treatment of HCC has been a challenge, and for many years was limited to the tyrosine kinase inhibitor sorafenib and to several novel tyrosine kinase inhibitors that have shown efficacy and have been approved. The current role of immune checkpoint inhibitors in the management of HCC, and how this role is likely to evolve in the years ahead, are key. Other than efforts evaluating single checkpoint inhibitors, potential combination strategies, including combinations with existing local and systemic approaches, including novel therapies are evolving. This is understandably of special interest considering the potential unique immune system of the liver, which may impact the use of immunotherapy in patients with HCC going forward, and how can it be enhanced further. Cancer 2019;125:3312-3319.

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Section: Immunotherapy-based Combinationsmentioning

confidence: 78%

Immune checkpoint inhibitors for hepatocellular carcinoma

Dika

Khalil

Abou‐Alfa

2019

Cancer

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“…Thus, immunotherapy may be particularly attractive following or combined with anti‐vascular endothelial growth factor (VEGF)‐targeted therapies. In line, preliminary data of pilot studies testing the combination of lenvatinib plus pembrolizumab (n = 26) and bevacizumab combined with atezolizumab (n = 68) showed encouraging response rates of 42% and 34% respectively …”

Section: Discussionmentioning

confidence: 99%

Programmed cell death protein‐1 (PD‐1)‐targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real‐world cohort

Scheiner¹,

Kirstein

Hucke³

et al. 2019

Aliment Pharmacol Ther

120

118

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Summary Background Programmed cell death protein‐1‐targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. Aim To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real‐world cohort of patients with advanced hepatocellular carcinoma. Methods Sixty‐five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut‐off) across six centres in Austria and Germany were retrospectively analysed. Results Child‐Pugh class A/B/C was 32 (49%)/28 (43%)/5 (8%). Immunotherapy was used as systemic first‐/second‐/third‐/fourth‐line treatment in 9 (14%)/27 (42%)/26 (40%)/3 (5%) patients. Fifty‐four patients had at least one follow‐up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12% and 49% respectively. Of 52 evaluable patients, four (8%) had hyperprogressive disease. Median time to progression was 5.5 (95% CI, 3.5‐7.4) months, median progression‐free survival was 4.6 (95% CI, 3.0‐6.2) months, and median overall survival was 11.0 (95% CI, 8.2‐13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child‐Pugh A and B patients; however, median overall survival (OS) was shorter in Child‐Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first‐/second‐line and third‐/fourth‐line respectively. Conclusions Programmed cell death protein‐1‐targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child‐Pugh stage B and patients with intensive pretreatment.

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“…This approach is based on the observation that objective response to ICP (expected in approximately one-third of all patients) translates into excellent survival 9 and is evident early. 10 Delaying the use of TACE to the time-point of progression (should this ever occur) and confining it to targeting of progressive lesions, will altogether reduce the number of patients and the proportion of liver parenchyma exposed to the collateral damage potentially caused by TACE. Most likely, however, this will not lessen the beneficial immunogenic effect of locoregional treatment, which is thought to be independent of the targeted tumour volume (abscopal effect).…”

Section: Immune Checkpoint Inhibitors: Use Them Early Combined and Imentioning

confidence: 99%

Immune checkpoint inhibitors: use them early, combined and instead of TACE?

Toni

2019

Gut

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Figure 1 Schematic representation of the development in the treatment of advanced-stage HCC based on median overall survival (mOS) data from some recent trials. The arrows are proportional to the reported (grey) or hypothetical (blue) mOS indicated by the respective numbers. The green overlapping arrows represent respectively the real-world and the expected survival (ie, based on the selection of 'ideal' candidates for TACE) in BCLC-B patients. The list of trials is not exhaustive and, due to the heterogeneity of patients' population, not suitable for direct cross-comparison between the trials. Atezo/Bev: combined atezolizumab and bevacizumab; pH, phase of clinical study; TACE, trans-arterial chemoembolisation.on July 7, 2020 by guest. Protected by copyright.

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Updated safety and clinical activity results from a phase Ib study of atezolizumab + bevacizumab in hepatocellular carcinoma (HCC)

Cited by 68 publications

References 0 publications

Immune checkpoint inhibitors for hepatocellular carcinoma

Immune checkpoint inhibitors for hepatocellular carcinoma

Programmed cell death protein‐1 (PD‐1)‐targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real‐world cohort

Immune checkpoint inhibitors: use them early, combined and instead of TACE?

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