Association between Adverse Events and Prognosis in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study

Abstract

This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longer survival (median survival time (MST): not reached vs. 14.3 months and not reached vs. 14.8 months, p = 0.001 and p = 0.047, respectively). In contrast, liver injuries were significantly correlated with shorter survival (MST: 14.7 months vs. not reached, p = 0.036), and the median development time was 21 days. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin–bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. The OS in the no discontinuation due to AE group was significantly longer than that in the discontinuation due to AEs group (MST not reached vs. 11.2 months, p = 0.001). We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments.

Significance of ramucirumab following atezolizumab plus bevacizumab therapy for hepatocellular carcinoma using real‐world data

“…Although the evidence for treatment post‐Atezo/Beva failure is still unclear, the most common second‐line therapies after Atezo/Beva treatment are LEN and SORA in real‐world practice 25–27 . A previous study reported that the median PFS was 6.1 and 2.5 months after progression to Atezo/Beva therapy in patients undergoing LEN and SORA treatment, respectively 27 .…”

“…24 Vascular endothelial growth factor-2 is known to be a receptor for Although the evidence for treatment post-Atezo/Beva failure is still unclear, the most common second-line therapies after Atezo/ Beva treatment are LEN and SORA in real-world practice. [25][26][27] A previous study reported that the median PFS was 6.1 and 2.5 months after progression to Atezo/Beva therapy in patients undergoing LEN and SORA treatment, respectively. 27 Lenvatinib has been shown to be a good sequential treatment option in patients with better hepatic reserve function 28 and it especially has a high response following Atezo/Beva treatment.…”

Prognostic biomarkers associated with immune checkpoint inhibitors in hepatocellular carcinoma

“…Immune tolerance imbalance and inflammatory side effects caused by ICIs are known as irAEs [114].The mechanism of irAEs is not well understood and may be related to the enhancement of systemic T cell activity by ICIs, which in turn leads to the loss of immune tolerance in individual organs [115]. Several studies [116][117][118] have shown that the occurrence of irAEs is associated with clinical benefit in HCC patients treated with ICIs and may be a potential biomarker for predicting clinical outcomes of ICI therapy in HCC patients. Xu et al [116] found that among 65 HCC patients receiving anti-PD-1 antibodies, the median PFS (302 days vs. 148 days, p = 0.004) and median OS (374 days vs. 279 days, p = 0.038) were better in the irAE group than in the non-irAE group.…”

The Association of Albumin-Bilirubin (ALBI) Grade with Mortality Risk in Trauma Patients with Liver Injuries

“…Patients who died had a significantly lower ALBI score than those who survived (2.8±0.4 vs 3.4±0.7, p < 0.001). Patients who died had a significantly lower GCS score (median [Q 1 -Q 3 ]; 8 [3][4][5][6][7][8][9][10][11][12][13] vs 15 [14][15], p < 0.001) but higher ISS (median [Q 1 -Q 3 ]; 33 [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] vs 20 [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], p < 0.001) than the surviving patients.…”

“…[12][13][14] The ALBI grade also functions as a useful and valuable predictor for outcomes in early stage and intermediate-stage hepatocellular, as well as in many systemic interventions or treatments for hepatocellular carcinoma. [15][16][17][18][19][20] It also functions as a crucial biomarker for the development of liver disease, reflecting the potential for hepatic failure and mortality from liver-related causes. [21][22][23][24][25][26][27] Patients with cholangiocarcinoma, 28 intrahepatic cholangiocarcinoma, 29 pancreatic cancer with liver metastases, 30 colorectal cancer with liver metastases, 31 and primary biliary cholangitis 32 can all benefit from knowing their ALBI grade as a prognostic indicator.…”