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Journal ArticleDOI

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice.

03 Jun 2021-Cancers (Multidisciplinary Digital Publishing Institute)-Vol. 13, Iss: 11, pp 2786
TL;DR: In this paper, the authors evaluated the efficacy and safety of atezolizumab plus bevacizumaab for patients with hepatocellular carcinoma (HCC).
Abstract: Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC. Materials and Methods: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs). Results: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs. Conclusion: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.
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Journal ArticleDOI
TL;DR: Patients who received atezolizumab plus bevacizumabs as 1st-line therapy had better clinical outcome than those who received in later lines, and the AFP response at 6 weeks could be a predictor of disease progression.
Abstract: Background. We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. Methods. A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. Results. The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6 weeks had a significantly longer TTP assessed by RECIST than those without an AFP response (P = 0.02). Conclusion. Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6 weeks could be a predictor of disease progression.

33 citations

Journal ArticleDOI
05 Aug 2021-Cancers
TL;DR: In this article, the early tumor response and safety of atezolizumab plus bevacizumaab for patients with unresectable hepatocellular carcinoma in real-world practice were investigated.
Abstract: The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37-649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.

22 citations

References
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Journal ArticleDOI
TL;DR: In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.
Abstract: Background No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. Methods In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Secondary outcomes included the time to radiologic progression and safety. Results At the second planned interim analysis, 321 deaths had occurred, and the study was stopped. Median overall survival was 10.7 months in the sorafenib group and 7.9 months in the placebo group (hazard ratio in the sorafenib group, 0.69; 95% confidence interval, 0.55 to 0.87; P<0.001). There was no significant difference between the two groups in the median time to symptomatic progression (4.1 months vs. 4.9 months, respectively, P=0.77). The median time to radiologic progression was 5.5 months in the sorafenib group and 2.8 months in the placebo group (P<0.001). Seven patients in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial response; no patients had a complete response. Diarrhea, weight loss, hand-foot skin reaction, and hypophosphatemia were more frequent in the sorafenib group. Conclusions In patients with advanced hepatocellular carcinoma, median survival and the time to radiologic progression were nearly 3 months longer for patients treated with sorafenib than for those given placebo.

10,074 citations

Journal ArticleDOI
TL;DR: A group of experts developed a set of guidelines aimed at providing a common framework for the design of clinical trials in HCC and adapted the concept of viable tumor-tumoral tissue showing uptake in arterial phase of contrast-enhanced radiologic imaging techniques-to formally amend RECIST, referred to herein as the modified RECIST assessment (mRECIST).
Abstract: The endpoint in cancer research is overall survival. Nonetheless, other potential surrogate endpoints, such as response rate and time to progression, are currently used. Measurement of response rate in hepatocellular carcinoma (HCC) has become a controversial issue. The World Health Organization (WHO) criteria underestimate the actual response rate; thus, they were amended in 2000 by a panel of experts convened by the European Association for the Study of the Liver (EASL) to take into account treatment-induced tumor necrosis. Applying these guidelines, there was an association between response rate and outcome prediction. More recently, the Response Evaluation Criteria in Solid Tumors (RECIST) guideline was proposed as a method for measuring treatment response based on tumor shrinkage, which is a valuable measure of antitumor activity of cytotoxic drugs. This method was initially adopted by regulatory agencies, such as the U.S. Food and Drug Administration (FDA), for drug approval. However, anatomic tumor response metrics can be misleading when applied to molecular-targeted therapies or locoregional therapies in HCC. In 2008, a group of experts convened by the American Association for the Study of Liver Diseases (AASLD) developed a set of guidelines aimed at providing a common framework for the design of clinical trials in HCC and adapted the concept of viable tumor-tumoral tissue showing uptake in arterial phase of contrast-enhanced radiologic imaging techniques-to formally amend RECIST. These amendments conformed the AASLD-JNCI (Journal of the National Cancer Institute) guidelines and are summarized and clarified in the current article. They are referred to herein as the modified RECIST assessment (mRECIST). Further studies are needed to confirm the accuracy of this measurement compared with conventional gold standards such as pathologic studies of explanted livers.

3,190 citations

Journal ArticleDOI
TL;DR: In patients with unresectable hepatocellular carcinoma, atezolIZumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib.
Abstract: Background The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinom...

3,085 citations

Journal ArticleDOI
TL;DR: A panel of therapeutic strategies to use, combine and develop to treat hot, altered and cold tumours is provided and the impact of combination therapy on the immune response to convert an immune cold into a hot tumour will be discussed.
Abstract: Immunotherapies are the most rapidly growing drug class and have a major impact in oncology and on human health. It is increasingly clear that the effectiveness of immunomodulatory strategies depends on the presence of a baseline immune response and on unleashing of pre-existing immunity. Therefore, a general consensus emerged on the central part played by effector T cells in the antitumour responses. Recent technological, analytical and mechanistic advances in immunology have enabled the identification of patients who are more likely to respond to immunotherapy. In this Review, we focus on defining hot, altered and cold tumours, the complexity of the tumour microenvironment, the Immunoscore and immune contexture of tumours, and we describe approaches to treat such tumours with combination immunotherapies, including checkpoint inhibitors. In the upcoming era of combination immunotherapy, it is becoming critical to understand the mechanisms responsible for hot, altered or cold immune tumours in order to boost a weak antitumour immunity. The impact of combination therapy on the immune response to convert an immune cold into a hot tumour will be discussed.

1,680 citations