BACKGROUND: This meta-analysis was dedicated to evaluating the effectiveness and safety of Atezolizumab plus Bevacizumab (Atez/Bev) and Lenvatinib (LEN) as first-line systematic therapy for unresectable hepatocellular carcinoma (u-HCC).
METHODS: The prospective protocol for this study was registered with the PROSPERO (Registration number: CRD42022356874). Literature searches were conducted in PubMed, EMBASE database Cochrane Library, and Web Science to determine all clinical controlled studies that reported Atez/Bev and LEN for treating u-HCC. We. evaluated as primary end-point overall survival (OS) and progression-free survival (PFS), as well as other outcomes such as tumor response and adverse events (AEs).Quality assessment and data extraction of studies were conducted independently by three reviewers. Mean difference (MD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. The meta-analysis was performed with RevMan 5.3 software.
RESULTS: 12 retrospective cohort studies (RCSs) involving a total of 4948 patients were finally included. The results showed that compared with LEN, Atez/Bev can improve the patient\'s PFS (HR = 0.80, 95% CI: 0.72 ~ 0.88; p < 0.0001) and reduce the rate of overall AEs (OR = 0.46 95% CI: 0.38 ~ 0.55, p < 0.00001) and grade ≥ 3 AEs (OR = 0.43; 95% CI: 0.36 ~ 0.51, p < 0.00001), while there is no difference between OS and treatment responses rate (objective response rate, disease control rate, complete response, partial response, progressive disease, and stable disease) between two groups. In addition, the subgroup analysis shows that Atez/Bev can promote the OS of patients with viral hepatitis. (HR = 0.79, 95% CI: 0.67 ~ 0.95; p = 0.01), while LEN has an advantage in improving OS in patients with Child-Pugh grade B liver function (HR = 1.98, 95% CI: 1.50 ~ 2.63; p < 0.00001).
CONCLUSIONS: Current evidence shows that compared with LEN, Atez/Bev has more advantages in PFS and safety in treating u-HCC and can improve the OS of patients with viral. LEN has advantages in improving the OS of patients with grade B liver function. However, more multicenter randomized controlled experiments are needed in the future to verify our results.

Scirrhous hepatocellular carcinoma (S-HCC) represents an uncommon subtype of HCC. During radiological evaluation this unique subtype is frequently mistaken as cholangiocarcinoma, fibrolamellar HCC, or metastatic adenocarcinoma. Here, we present the case of a 50-year-old woman with a large hepatic mass. A triple-phase computed tomography of the liver revealed an arterial enhancing lesion without portovenous washout at hepatic segment 4a/8. The liver biopsy showed hepatocellular characteristics and was positive for Hep Par 1, CK7, CK19, Arginase 1 and CEA, indicating atypical S-HCC. This patient had achieved tumor control with combined treatment with atezolizumab plus bevacizumab and was then treated with lenvatinib after tumor progression. The patient died 15 months after the initial diagnosis.

BACKGROUND: Atezolizumab (ATZ) plus bevacizumab (BVC) co-administration is one of the newest systemic interventions in advanced hepatocellular carcinoma (AHCC). This treatment approach is more costly and effective than other therapeutic interventions, significantly improving AHCC survival and health-related quality of life.
OBJECTIVE: This economic study aimed to systematically review all cost-effectiveness analyses of ATZ/BVC combination in AHCC.
METHODS: A comprehensive search in scientific databases was performed using a highly sensitive syntax to find all related economic evaluations. The target population was AHCC patients. The intervention was ATZ/BVC, which was compared with sorafenib, nivolumab, and other anticancer strategies. We included studies that reported quality-adjusted life-years (QALYs) and/or life-years, costs, and incremental cost-effectiveness ratio (ICER), and finally, the characteristics of included studies were categorized.
RESULTS: Out of 315 identified records, 12 cost-effectiveness analyses were eligible for inclusion in the systematic review. Treatment costs were significantly higher with ATZ/BVC in all studies (from 61,397 to 253,687 USD/patient compared to sorafenib and nivolumab, respectively). Incremental QALYs/patient varied from 0.35 to 0.86 compared to sintilimab/BVC and sorafenib. Although ICERs for drugs varied widely, all were united in the lack of cost-effectiveness of the ATZ/BVC. The willingness-to-pay threshold in all studies was lower than the ICER, which indicated a reluctance to pay for this treatment strategy by the health systems.
CONCLUSIONS: The ATZ/BVC combination is an expensive targeted immunotherapy in AHCC. Significant discounts in ATZ and BVC prices are essential for this novel approach to be cost-effective and extensively used.

UNASSIGNED: Non-small cell lung cancer (NSCLC) stands as one of the most prevalent types of cancer worldwide, driving extensive research in oncologic therapeutic approaches. Atezolizumab, among the treatments under scrutiny, is undergoing evaluation as a potential first-line therapy for NSCLC. This review aims to assess the efficacy of atezolizumab in treating patients with NSCLC and to shed light on the ongoing quest for the most effective treatment.
UNASSIGNED: Multiple scientific databases, including PubMed, Cochrane, and ScienceDirect, were consulted. The literature identification utilized the strategic Boolean term method of keywords relating to \"non-small cell lung cancer\" and \"atezolizumab\" to suggest the analyzed population in our review without restricting the potential outcomes. The primary inclusion criterion is clinical studies that attempted to determine the efficacy of atezolizumab in NSCLC patients.
UNASSIGNED: We included four trials to be analyzed in the final analysis, which we stratified into the programmed cell death-ligand 1 (PD-L1) expressivity status aside from the pooled intention-to-treat (ITT) population. We found the addition of atezolizumab may significantly improve the overall survival (OS) in the respective arm, remarkably among the high PD-L1 expression group (TC3 or IC3). The result of our meta-analysis presented the pooled OS of 0.79 (0.72, 0.87) in 95% confidence interval (CI) with a P value of < 0.05. Sub-analysis of the PD-L1\'s expression revealed TC3 population benefits the most (hazard ratio (HR): 0.55, 95% CI (0.42, 0.73)), compared to low (HR: 0.80, 95% CI (0.68, 0.93)) and negative expression (HR: 0.79, 95% CI (0.68, 0.93)); which is statistically meaningful (P < 0.05). Similar result was also observed in progression-free survival (PFS) analysis with the HR value of 0.63 (0.55, 0.72), with P value of < 0.05, favoring atezolizumab arm.
UNASSIGNED: Upon examination, the study reveals that the addition of atezolizumab demonstrates notable improvements in both OS and PFS among NSCLC patients. These findings present promising attributes for atezolizumab as a viable treatment for NSCLC. However, it is important to acknowledge that the future holds further revelations in this realm, and more insights are yet to be uncovered.

The combination regimen of atezolizumab plus bevacizumab (Atezo/Bev) is currently used as first-line treatment in patients with unresectable hepatocellular carcinoma. Herein, we report a rare case of curative hepatic resection performed as conversion surgery in a patient with intermediate-stage hepatocellular carcinoma following preoperative Atezo/Bev therapy. After five treatment cycles of Atezo/Bev therapy, followed by four cycles of atezolizumab monotherapy, the tumor marker levels decreased to baseline levels and 22 small daughter nodules disappeared, leaving only the primary tumor. Therefore, we performed resection of the primary tumor as conversion surgery, and postoperative histopathology confirmed complete tumor necrosis. No cancer recurrence has been observed until the 5-month postoperative follow-up, and the patient remains drug free. Consistent with the findings in this case, a review of previously reported cases revealed that in cases of successful conversion surgery, neoadjuvant Atezo/Bev therapy was associated with intra-tumoral bleeding, immune-related adverse events, and normalization of the tumor marker levels.

UNASSIGNED: In 2020, atezolizumab-bevacizumab became the new standard of care (SOC) for first-line unresectable hepatocellular carcinoma (HCC) patients, following a decade where sorafenib was the preferred first-line treatment. In the last few years, a number of novel systemic treatments with non-inferiority and superiority to sorafenib have been approved as first-line treatments.
UNASSIGNED: The objective of this systematic literature review (SLR) and network meta-analysis (NMA) was to compare randomised controlled trial evidence for atezolizumab-bevacizumab with globally relevant pharmacological comparators for first-line treatment of patients with unresectable HCC.
UNASSIGNED: Randomised controlled trials investigating first-line treatment of HCC in adults with no prior systemic treatment were eligible for inclusion into the SLR and were retrieved from Embase, MEDLINE, and Evidence-Based Medicine (EBM) Reviews. Interventions of interest for the NMA included atezolizumab-bevacizumab, sorafenib, lenvatinib, durvalumab (including in combination with tremelimumab), cabozantinib (including in combination with atezolizumab), camrelizumab (including in combination with rivoceranib), pembrolizumab (including in combination with lenvatinib), and tislelizumab. Random effects NMA was conducted for survival endpoints within a Bayesian framework with an informative prior distribution for between-study heterogeneity. The hazard ratios for relative treatment effect were estimated with 95% credible intervals (CrIs).
UNASSIGNED: The SLR identified 49 studies, of which eight formed a connected evidence network permitting the indirect treatment comparison of atezolizumab-bevacizumab with comparators of interest. The indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus most comparators. All indirect treatment comparison results for atezolizumab-bevacizumab included the null value within the 95% CrI (n = 1) for OS and progression-free survival (PFS).
UNASSIGNED: The results of the NMA indicate atezolizumab-bevacizumab is associated with superior or comparable OS and PFS together with a manageable safety profile compared with globally relevant comparators in the unresected HCC indication. The findings support that atezolizumab-bevacizumab remains SOC for the management of first-line unresectable HCC patients.

Several successful attempts have been recorded with PD-L1 blockade via atezolizumab monotherapy or combination therapy with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). Due to the lack of a large-scale study, we present a meta-analysis aimed at evaluating the safety and efficacy of this promising strategy in patients with mTNBC.
A comprehensive literature search was conducted using electronic databases to identify eligible RCTs. Twelve studies, including 2479 mTBNC patients treated with atezolizumab monotherapy or in combination with chemotherapy, were included up to January 2022. The PRISMA checklist protocol and the I2 statistic were applied for quality assessment and heterogeneity tests of the selected trials, respectively. Fixed and random-effects models were estimated based on the heterogeneity tests, and statistical analysis was performed using CMA.
Our pooled findings demonstrated that the median overall survival (OS) and progression-free survival (PFS) were 16.526 and 5.814 months in mTNBC patients, respectively. Furthermore, when comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, mTNBC patients with PD-L1 had better OS, PFS, and ORR than PD-L1-negative patients. Also, the immune-related adverse event incident for alopecia was higher (51.9%) than other complications across atezolizumab therapy.
Moreover, the pooled analysis indicated that the overall rate of lung metastasis following atezolizumab therapy was 42.8%, which was higher than the rates of metastasis in bone (26.9%), brain (5.4%), and lymph node (6.5%). Atezolizumab showed a manageable safety profile and had promising and durable anti-tumor efficacy in TMBC patients. Higher PD-L1 expression may be closely correlated with better clinical efficacy.

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UNASSIGNED: Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC.
UNASSIGNED: A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes.
UNASSIGNED: A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis.
UNASSIGNED: Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.

BACKGROUND: Atezolizumab plus bevacizumab and lenvatinib are the current first-line systematic therapy for unresectable hepatocellular carcinoma (uHCC). However, the selection of initial treatment among the two therapies are controversial. This meta-analysis aims to compare efficacy and safety between atezolizumab plus bevacizumab and lenvatinib.
METHODS: We systematically searched for studies on atezolizumab plus bevacizumab and lenvatinib in the online databases PubMed, Embase, Web of Science and Cochrane Library. The outcome data including overall survival (OS), progression free survival (PFS), tumor response and adverse events (AEs), were independently extracted by two authors in a standardized way.
RESULTS: Eight retrospective cohort studies with 3690 patients (atezolizumab plus bevacizumab: 1680, lenvatinib: 2010) were included in the meta-analysis. The atezolizumab plus bevacizumab group had significant longer PFS [hazard ratio (HR) 0.76, 95% confidence intervals (CI) 0.65-0.88; I squared statistic (I2) = 0.0%, p = 0.590], compared with lenvatinib group but no significant difference in OS (HR 0.87, 95% CI 0.75-1.01; I2 = 0.0%, p = 0.597), objective response rate (ORR) [risk ratio (RR) 0.89, 95% CI 0.79-1.02; I2 = 19.3%, p = 0.283] and disease control rate (DCR) (RR 1.03, 95% CI 0.98-1.09; I2 = 0.0%, p = 0.467) among them. Moreover, patients receiving atezolizumab plus bevacizumab exhibited lower incidences of grade 3/4 AEs than those receiving lenvatinib (RR 0.65, 95% CI 0.51-0.83; I2 = 69.3%, p = 0.003). However, in non-viral patients group, lenvatinib delivered favorable outcomes in OS (HR 1.32, 95% CI 1.04-1.67; I2 = 0.0%, p = 0.380) compared with atezolizumab plus bevacizumab.
CONCLUSIONS: Atezolizumab plus bevacizumab provides potential advantage in efficacy and better safety than lenvatinib in the treatment of uHCC. Lenvatinib is an appropriate effective alternative to atezolizumab plus bevacizumab in patients without viral infecting.