Atezolizumab plus bevacizumab and tremelimumab plus durvalumab: how should we choose these two immunotherapy regimens for advanced hepatocellular carcinoma?
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ABSTRACT:
SUBMITTER: Hatanaka T
PROVIDER: S-EPMC9745629 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
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Atezolizumab plus bevacizumab and tremelimumab plus durvalumab: how should we choose these two immunotherapy regimens for advanced hepatocellular carcinoma?
Hatanaka Takeshi T Naganuma Atsushi A Yata Yutaka Y Kakizaki Satoru S
Hepatobiliary surgery and nutrition 20221201 6
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Project description: Not available
| S-EPMC9396100 | biostudies-literature
Project description:BackgroundAtezolizumab plus bevacizumab (Ate/Bev) demonstrated promising efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III IMbrave150 trial. However, patients with Child-Pugh B HCC were excluded in the abovementioned prospective trial. Therefore, we aimed to investigate the efficacy and safety of Ate/Bev in patients with Child-Pugh B HCC.MethodsThis multicenter retrospective study included 36 patients with Child-Pugh B advanced HCC who received Ate/Bev at four cancer referral centers between May 2020 and August 2021. Comparative analyses were performed with an independent cohort of patients with Child-Pugh A HCC from the same registry (n = 133).ResultsAll patients received Ate/Bev as first-line systemic treatment for advanced HCC. The objective response and disease control rates of patients in the Child-Pugh groups B and A were 11.1% and 58.3% and 34.6% and 76.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.0 months [95% confidence interval (CI), 1.7-4.3) and 7.7 months (95% CI, 4.8-10.6) in the Child-Pugh B group, whereas the median PFS and OS were 9.6 months (95% CI, 5.1-14.2) and not reached (95% CI, not available) in the Child-Pugh A group, respectively. Compared to the Child-Pugh A group, grade 3-4 adverse events (AEs) were more common in the Child-Pugh B group (44.4% versus 15.8, p < 0.001), with the most frequent grade 3-4 AEs being gastrointestinal bleeding (n = 6, 16.7%), neutropenia (n = 5, 13.9%), and thrombocytopenia (n = 4, 11.1%).ConclusionsIn the Child-Pugh B subgroup of patients with advanced HCC, Ate/Bev treatment showed modest clinical activity. However, due to the increased frequency of serious AEs, careful evaluation of treatment response and AE management is required in this subgroup of patients.
| S-EPMC10495918 | biostudies-literature
Project description:In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.
| S-EPMC8327224 | biostudies-literature
Project description:Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child-Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50-13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82-9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19-11.82) and the median PFS was 6.50 months (95% CI, 3.93-9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations.
| S-EPMC10887033 | biostudies-literature
Project description:Background/aimRadiotherapy (RT) is an effective local treatment for hepatocellular carcinoma (HCC). However, whether additional RT is safe and effective in patients with advanced HCC receiving atezolizumab plus bevacizumab remains unclear. This retrospective cohort study aimed to evaluate the feasibility of additional RT in these patients.MethodsBetween March and October 2021, we retrospectively analyzed seven patients with advanced HCC who received RT during treatment with atezolizumab plus bevacizumab. The median prescribed RT dose was 35 Gy (range, 33-66). Freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) after RT were analyzed.ResultsThe median follow-up duration after RT was 14.2 months (range, 10.0-18.6). Of the seven patients, disease progression was noted in six (85.7%), the sites of disease progression were local in two (28.6%), intrahepatic in four (57.1%), and extrahepatic in four (57.1%). The median time of FFLP was not reached, and PFS and OS times were 4.0 (95% confidence interval [CI], 3.6-4.5) and 14.8% (95% CI, 12.5-17.2) months, respectively. The 1-year FFLP, PFS, and OS rates were 60% (95% CI, 43.8-76.2), 0%, and 85.7% (95% CI, 75.9-95.5), respectively. Grade 3 or higher hematologic adverse events (AEs) were not observed, but grade 3 nonhematologic AEs unrelated to RT were observed in one patient.ConclusionsThe addition of RT may be feasible in patients with advanced HCC treated with atezolizumab plus bevacizumab. However, further studies are required to validate these findings.
| S-EPMC10565546 | biostudies-literature
Project description:Background and aimsTreatment with atezolizumab and bevacizumab has been approved as one of the standards of care for patients with advanced hepatocellular carcinoma (HCC). The median overall survival (OS) upon available treatments still remains below 2 years, urgently suggesting better stratification tools to identify ideal candidates for this treatment and potentially allowing personalized approaches. In this study, we evaluated the potential role of extracellular vesicles (EVs) as a novel biomarker in patients receiving atezolizumab and bevacizumab for HCC.MethodsWe characterized EVs in 212 longitudinal serum samples from an observational cohort of 53 individuals with advanced HCC, who started therapy with atezolizumab plus bevacizumab at our center between January 2020 and March 2022.ResultsIn our cohort, the overall efficacy of atezolizumab and bevacizumab was comparable to previously published phase III data. We detected significantly smaller EVs in treatment responders, while enlarged EVs were associated with significantly decreased efficacy of atezolizumab and bevacizumab in terms of OS. A decrease in vesicle size during immunotherapy was related to a longer progression-free survival (PFS). A univariate Cox regression analysis including various clinicopathological parameters (e.g., tumor stage, markers of inflammation, organ dysfunction, or tumor markers) revealed vesicle size as an independent prognostic marker in HCC patients receiving atezolizumab and bevacizumab. Moreover, higher vesicle concentrations and lower zeta potentials were identified as a positive prognostic factor throughout treatment.ConclusionsDistinct EV characteristics such as vesicle size, concentration, and zeta potential represent promising novel biomarkers in patients with advanced HCC receiving atezolizumab and bevacizumab, potentially helping to identify optimal candidates for checkpoint inhibitor-based treatments.
| S-EPMC11545167 | biostudies-literature
Project description:Background and objectiveHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, especially in China. According to the 2021 Chinese Society of Clinical Oncology guidelines, sorafenib, lenvatinib, atezolizumab combined with bevacizumab, and sintilimab combined with bevacizumab are recommended as first-line treatment options for advanced HCC. This study provides a cost-effectiveness analysis of these treatments from the patient perspective.MethodsA partitioned survival model was established using the TreeAge 2019 software to evaluate the cost-effectiveness. The model includes three states, namely progression-free survival, progressive disease, and death. Clinical data were derived from three randomized controlled studies involving patients with advanced HCC who received the following treatment: sorafenib and lenvatinib (NCT01761266); atezolizumab in combination with bevacizumab (NCT03434379); and sintilimab in combination with bevacizumab (NCT03794440). Cost and clinical preference data were obtained from the literature and interviews with clinicians.ResultsAll compared with sorafenib therapy, lenvatinib had an incremental cost-effectiveness ratio (ICER) of US$188,625.25 per quality-adjusted life year (QALY) gained; sintilimab plus bevacizumab had an ICER of US$75,150.32 per QALY gained; and atezolizumab plus bevacizumab had an ICER of US$144,513.71 per QALY gained. The probabilistic sensitivity analysis indicated that treatment with sorafenib achieved a 100% probability of cost-effectiveness at a threshold of US$36,600/QALY. One-way sensitivity analysis revealed that the results were most sensitive to the medical insurance reimbursement ratio and drug prices.ConclusionsIn this economic evaluation, therapy with lenvatinib, sintilimab plus bevacizumab, and atezolizumab plus bevacizumab generated incremental QALYs compared with sorafenib; however, these regimens were not cost-effective at a willingness-to-pay threshold of US$36,600 per QALY. Therefore, some patients may achieve preferred economic outcomes from these three therapies by tailoring the regimen based on individual patient factors.
| S-EPMC10064722 | biostudies-literature
Project description: Not available
| S-EPMC11791609 | biostudies-literature
Project description:Background & aimsThe combination of atezolizumab and bevacizumab offers a novel approach to immunomodulation, showing efficacy as a primary treatment in advanced hepatocellular carcinoma (HCC). Concerns about graft safety and rejection have limited its exploration in the neoadjuvant setting of liver transplantation (LT). In this study, we investigate the clinical efficacy and the safety profile of pre-transplant administration of atezolizumab and bevacizumab for HCC.MethodsHerein, we performed a prospective assessment of 17 patients with HCC treated with neoadjuvant preoperative atezolizumab and bevacizumab prior to LT for HCC, obtained from December 2020 and December 2023 at seven Western transplant centers.ResultsAmong the 17 patients with HCC included in the study, 16 (94.1%) had a tumor burden outside of Milan criteria. Neoadjuvant locoregional therapies along with the administration of atezolizumab plus bevacizumab (median: 5 months; discontinued at least 4 weeks prior to LT) led to an objective response rate of 94% (complete response: 59%), downstaging to within Milan criteria (82%) and a pathological response at explant examination of 88%. Grade 3-4 treatment-related adverse events accounted for 17.6% of cases and were manageable. During the 25-month median follow-up period, two cases of mild (rejection activity index ≤4), biopsy-proven rejection were reported but no instances of severe allograft rejection or graft loss were reported. The 1-year and 3-year post-LT survival rates were 94.2% and 88.2%, respectively.ConclusionsThis study highlights the favorable oncological and survival outcomes associated with atezolizumab and bevacizumab treatment in the pre-LT setting. This immune-based combination was safe in terms of treatment-related adverse events, and absence of severe post-transplant rejection or graft loss. These preliminary results could pave the way for expanding transplant eligibility criteria in patients at more advanced HCC stages.Impact and implicationsStudies on the combination of atezolizumab and bevacizumab in the neoadjuvant setting prior to liver transplantation for hepatocellular carcinoma have been limited, despite its potential to enhance anti-tumor responses and downstaging, owing to concerns about its safety profile. Among 17 patients who underwent successful liver transplantation following neoadjuvant atezolizumab/bevacizumab, 82% achieved downstaging to within Milan criteria, 94% radiological objective response and 88% pathology response, without drop-outs due to treatment-related adverse events or graft loss. The neoadjuvant combination of atezolizumab plus bevacizumab prior to liver transplantation for hepatocellular carcinoma shows an encouraging safety profile and stands out as a promising pre-transplant optimization treatment, leading to improved oncological outcomes.
| S-EPMC11794155 | biostudies-literature
Project description:BackgroundAlthough atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u-HCC), changes in hepatic function during therapy have yet to be reported.AimThis retrospective clinical study aimed to elucidate early responses to Atez/Bev.MethodsFrom September 2020 to April 2021, 171 u-HCC patients undergoing Atez/Bev treatment were enrolled (BCLC stage A:B:C:D = 5:68:96:2). Of those, 75 had no prior history of systemic treatment. Relative changes in hepatic function and therapeutic response were assessed using albumin-bilirubin (ALBI) score and Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1, respectively.ResultsIn initial imaging examination findings, objective response rates for early tumor shrinkage and disease control after 6 weeks (ORR-6W/DCR-6W) were 10.6%/79.6%. Similar response results were observed in patients with and without a past history of systemic treatment (ORR-6W/DCR-6W = 9.7%/77.8% and 12.2%/82.9%), as well as patients in whom Atez/Bev was used as post-progression treatment following lenvatinib (ORR-6W/DCR-6W = 7.7%/79.5%), for which no known effective post-progression treatment has been established. In 111 patients who underwent a 6-week observation period, ALBI score was significantly worsened at 3 weeks after introducing Atez/Bev (-2.525 ± 0.419 vs -2.323 ± 0.445, p < .001), but then recovered at 6-weeks (-2.403 ± 0.452) as compared to 3-weeks (p = .001). During the observation period, the most common adverse events were appetite loss (all grades) (12.3%), general fatigue/hypertension (all grades) (11.1%, respectively), and urine protein (all grades) (10.5%).ConclusionAtez/Bev might have therapeutic potential not only as first but also later-line treatment of existing molecular target agents. In addition, this drug combination may have less influence on hepatic function during the early period, as the present patients showed a good initial therapeutic response.
| S-EPMC8842687 | biostudies-literature