Efficacy and safety of Atezolizumab plus Bevacizumab-based sequential treatment for unresectable hepatocellular carcinoma: a simulation model

Celsa, Ciro; Cabibbo, Giuseppe; Battaglia, Salvatore; Giuffrida, Paolo; Rizzo, Giacomo Emanuele Maria; Grova, Mauro; Giacchetto, Marco; Rancatore, Gabriele; Stornello, Caterina; Grassini, Maria Vittoria; Badalamenti, Giuseppe; Enea, Marco; Craxı̀, Antonio; Marco, V. Di; Cammà, Calogero

doi:10.1016/s0168-8278(22)01128-x

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…77,78 Interestingly, lenvatinib and sorafenib appeared as the most effective options in second line and the sequence sorafenib–cabozantinib after atezolizumab plus bevacizumab reached a median OS of 28 months in the previously mentioned simulation model. 78,79 Similarly, ramucirumab, regorafenib, and cabozantinib were proven effective and safe following immunotherapy, also when received beyond the second line of therapy. 80–82 Of note, ramucirumab was offered to a sorafenib-naïve population with baseline AFP levels ⩾400 ng/mL, 64% of whom received a prior line of therapy containing ICIs, whereas regorafenib and cabozantinib were given to a sorafenib-experienced population, 9% and 10% of whom, respectively, received prior immunotherapy.…”

Section: The Reshaped Therapeutic Algorithm: How To Inform Treatment ...mentioning

confidence: 99%

Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?

et al. 2023

View full text Add to dashboard Cite

The treatment landscape of advanced hepatocellular carcinoma (HCC) has broadened with immune checkpoint inhibitors (ICIs) setting a novel standard of care. With the increased number of therapies either in first or in further line, disentangling the possible treatment sequences has become much more complex. Yet, all the second-line therapies have been evaluated after sorafenib. After ICIs, offering multikinase inhibitors is a widespread approach, either shifting forward sorafenib or lenvatinib, or choosing among regorafenib or cabozantinib, already approved in the refractory setting. Under specific circumstances, ICIs could be maintained beyond disease progression in patients with proven clinical benefit, as supported by some data emerging from phase III clinical trials with immunotherapy in HCC. Rechallenge with ICIs is an additional attractive alternative, although requiring careful and individual evaluation as efficacy and safety of such a strategy have not been yet clarified. Still, a considerable number of patients displays primary resistance to ICIs and might benefit from antiangiogenics either alone or in addition to ICIs instead. Hopefully, the ongoing clinical trials will enlighten regarding the most effective treatment pathways. The identification of predictive correlates of response to immunotherapy will help treatment allocation at each stage, thus representing an urgent matter to address in HCC research. With programmed death ligand 1 expression, tumor mutational burden, and microsatellite status being inadequate biomarkers in HCC, patient characteristics, drug safety profile, and regulatory approval remain key elements to acknowledge in routine practice. Despite the tissue remaining a preferred source, biomarkers discovery could take advantage of liquid biopsy to overcome the matter of tissue availability and track tumor changes. Lastly, tumor genetic phenotypes, tumor microenvironment features, gut microbiome, and markers of immune response and systemic inflammation are all potential emergent predictors of response to ICIs, pending validation in the clinical setting.

show abstract

Section: The Reshaped Therapeutic Algorithm: How To Inform Treatment ...mentioning

confidence: 99%

Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?

et al. 2023

View full text Add to dashboard Cite

show abstract

“…For these reasons, PFS could be useful to evaluate the effectiveness of sequential therapies in settings where multiple treatment lines are available. Based on this assumption, the patient’s journey could be represented as the sum of multiple subsequent PFSs of sequential treatment lines ( Figure 2 ) [ 21 , 25 , 39 ]. The use of PFS was initially discouraged in HCC trials due to the risk of competing events and the coexistence of cancer and underlying liver disease.…”

Section: Clinical and Radiological Endpoints In Hccmentioning

confidence: 99%

The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints

et al. 2022

Self Cite

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a challenging malignancy characterised by clinical and biological heterogeneity, independent of the stage. Despite the application of surveillance programs, a substantial proportion of patients are diagnosed at advanced stages when curative treatments are no longer available. The landscape of systemic therapies has been rapidly growing over the last decade, and the advent of immune-checkpoint inhibitors (ICIs) has changed the paradigm of systemic treatments. The coexistence of the tumour with underlying cirrhosis exposes patients with HCC to competing events related to tumour progression and/or hepatic decompensation. Therefore, it is relevant to adopt proper clinical endpoints to assess the extent of treatment benefit. While overall survival (OS) is the most accepted endpoint for phase III randomised controlled trials (RCTs) and drug approval, it is affected by many limitations. To overcome these limits, several clinical and radiological outcomes have been used. For instance, progression-free survival (PFS) is a useful endpoint to evaluate the benefit of sequential treatments, since it is not influenced by post-progression treatments, unlike OS. Moreover, radiological endpoints such as time to progression (TTP) and objective response rate (ORR) are frequently adopted. Nevertheless, the surrogacy between these endpoints and OS in the setting of unresectable HCC (uHCC) remains uncertain. Since most of the surrogate endpoints are radiology-based (e.g., PFS, TTP, ORR), the use of standardised tools is crucial for the evaluation of radiological response. The optimal way to assess the radiological response has been widely debated, and many criteria have been proposed over the years. Furthermore, none of the criteria have been validated for immunotherapy in advanced HCC. The coexistence of the underlying chronic liver disease and the access to several lines of treatments highlight the urgent need to capture early clinical benefit and the need for standardised radiological criteria to assess cancer response when using ICIs in mono- or combination therapies. Here, we review the most commonly used clinical and radiological endpoints for trial design, as well as their surrogacy with OS. We also review the criteria for radiological response to treatments for HCC, analysing the major issues and the potential future perspectives.

show abstract

Efficacy and safety of Atezolizumab plus Bevacizumab-based sequential treatment for unresectable hepatocellular carcinoma: a simulation model

Cited by 2 publications

References 0 publications

Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?

Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?

The Evolving Scenario in the Assessment of Radiological Response for Hepatocellular Carcinoma in the Era of Immunotherapy: Strengths and Weaknesses of Surrogate Endpoints

Contact Info

Product

Resources

About