Atezolizumab, a humanized antiprogrammed death ligand 1 monoclonal immunoglobulin G1 antibody, is a targeted therapeutic drug known as an immune checkpoint inhibitor. It is currently used to treat various types of cancer, including unresectable hepatocellular carcinoma (HCC), nonsmall cell lung cancer, urothelial cancer, and breast cancer, and is becoming a therapeutic option in the forefront of oncology treatment. However, it may sometimes lead to undesirable adverse reactions owing to the activation of immune responses in various organs. Cutaneous adverse reactions to atezolizumab are well known; however, cases of anaphylaxis are very rare. In this report, we present the first case of HCC who experienced near-fatal anaphylaxis to atezolizumab in South Korea.

BACKGROUND: Platinum-based chemotherapy represents the standard of care (SoC) for the first-line treatment of advanced urothelial carcinoma (mUC). The benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy was recently investigated. We performed an individual patient data (IPD) meta-analysis of phase 3 clinical trials comparing ICI-based treatments.
METHODS: A systematic literature search was conducted on the MEDLINE and CENTRAL databases. The results were filtered by including only reports on clinical trials or randomized clinical trials from 2018 to 2023, including 3047 patients from four clinical trials (EV302, CHECKMATE-901, IMVIGOR130, KEYNOTE-361). An IPD meta-analysis was performed by reconstructing IPD from Kaplan-Meier curves. The primary endpoints were overall survival (OS) and progression-free survival (PFS) of Pembrolizumab + EV compared to experimental arms of the other trials of immunotherapy + chemotherapy.
RESULTS: The OS analysis showed an advantage of IPD from EV302 vs. all the other trials. For EV302 vs. KEYNOTE-361, the HR was 0.51; for EV302 vs. IMVIGOR130, the HR was 0.47; and for EV302 vs. CHECKMATE-901, the HR was 0.66 (CI 95% 0.51-0.85). In the PFS analysis, the EV302 arm showed a statistically significant advantage compared to CHECKMATE-901 (HR 0.66) and versus IMVIGOR130 (HR 0.51).
CONCLUSIONS: By using reconstructed IPD curves, it was not possible to adjust patient-level covariates, and the heterogeneity of the included population may have affected the pooled results.
CONCLUSIONS: The EV302 experimental arm showed better OS and PFS when compared to the other immunochemotherapy combinations. An immunochemotherapy combination strategy at the beginning of treatment in mUC seems to be superior in terms of OS and PFS compared to platinum-based chemotherapy alone. EV-Pembrolizumab resulted to have better outcomes compared to avelumab, rather than other immunochemotherapy combinations. However, given the heterogeneity of these studies, a longer follow up and prospective trials are needed to confirm these data.

Treatment with atezolizumab and bevacizumab is the first-line therapy for unresectable hepatocellular carcinoma. Although immune checkpoint inhibitors are novel and effective treatments, they can induce immune-related adverse events. However, neurological immune-related adverse events have rarely been reported. We report the case of a man in his 40s with hepatocellular carcinoma who developed life-threatening encephalitis after atezolizumab plus bevacizumab was administered. The patient presented with fever, headache, altered mentality, and general epileptic seizures, ten days after administration. Cerebrospinal fluid analysis showed elevated white blood cells and elevated protein levels, but revealed no infection or malignancy. Brain magnetic resonance imaging showed diffuse leptomeningeal enhancement in both the cerebrum and cerebellum. As immune checkpoint inhibitor-induced encephalitis was strongly suspected, steroid pulse therapy was initiated and neurological symptoms quickly improved. The patient was discharged after 66 days of hospitalization, and administration of sorafenib and radiotherapy was started for the hepatocellular carcinoma on an outpatient basis. This case demonstrates the importance of recognizing neurological immune-related adverse events following atezolizumab and bevacizumab treatment for early intervention. We discuss this case in comparison to available literature and previous two cases of Atezolizumab- and bevacizumab- induced encephalitis in hepatocellular carcinoma.

A woman in her early 80 s was followed up in our hospital for chronic hepatitis C after viral eradication. We detected rapid-growing lymph node metastasis of hepatocellular carcinoma (HCC) after treatment with transcatheter arterial chemoembolization and/or radiofrequency ablation. We found that the metastasis was operable, but the size and location of the metastasis obliged the patient to receive pancreatoduodenectomy, which was too invasive. Then we initiated systemic chemotherapy to perform radical minimally invasive surgery. We treated the patient with 3 weekly cycles of atezolizumab 1200 mg plus bevacizumab 15 mg/kg. The patient tolerated the treatment well, and treatment-emergent adverse events included deterioration of hypertension and increased uric protein. After a total of 4 cycles of therapy, abdominal computed tomography findings showed that the metastasis evidently decreased, and a complete response was achieved based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1). Seventeen days later, the metastasis was dissected. Subsequently, we confirmed that there was no pathological metastatic lesion in the resected lymph node. Our case is the first report of successful application of the radical therapy to lymph node metastasis of HCC via combination therapy with atezolizumab/bevacizumab.

Immune checkpoint inhibitor (ICI)-related type 1 diabetes is an immune-related adverse event (irAE), occurring in slightly less than 1% of patients undergoing ICI therapy. Most cases develop during ICI treatment, with occurrences long after discontinuation being extremely rare. A 76-year-old woman, with no history of glucose tolerance issues, was diagnosed with lung adenocarcinoma with pleural invasion and underwent chemotherapy, including atezolizumab, an anti-programmed death-ligand 1 antibody. This treatment was discontinued due to disease progression, although she continued with other chemotherapy regimens. Approximately 5.5 months (166 days) after her last atezolizumab dose, she developed diabetic ketoacidosis, fulfilling the diagnostic criteria for fulminant type 1 diabetes. Anti-glutamic acid decarboxylase antibodies were positive. The patient carried susceptibility human leukocyte antigen (HLA) haplotypes, which are associated with type 1 diabetes. To date, including our patient, only nine cases of ICI-related type 1 diabetes developed after ICI discontinuation have been precisely reported. Eight cases originated from East Asia, with six exhibiting fulminant type 1 diabetes, and seven tested negative for islet-related autoantibodies. The reported cases were independent of ICI types, cycle number, or HLA haplotypes. Median time from the last ICI administration to diabetes onset was 4 months (range: 2-7 months). Although reports of cases occurring after ICI discontinuation are currently limited, their frequency may increase with the wider use of ICIs and improved survival rates of patients post-treatment. Therefore, it is crucial to remain vigilant for the development of ICI-related type 1 diabetes, not only during ICI administration, but also long after discontinuation.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13340-024-00719-4.

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.