Adverse events of immune checkpoint inhibitors in hepatocellular carcinoma: a systemic review and meta-analysis

Tian, Jin-Cheng; Liu, Hui; Yan, Lun-Jie; Ding, Zi-Niu; Han, Chen; Tian, Bao-Wen; Tan, Siyu; Dong, Zhao‐Ru; Wang, Dongxu; Xue, Jun-Shuai; Mao, Xin-Cheng; Yan, Yu-Chuan; Li, Tao

doi:10.1007/s10238-022-00938-6

Cited by 8 publications

(9 citation statements)

References 84 publications

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“…With regard to ICIs, which were introduced in recent years, the appearance of immune‐related AEs in patients with lung cancer or malignant melanoma indicates activation of the patient's immune response, which contributes to the antitumor effect and prolonged OS 13–16 . Regarding HCC, although the significance of immune‐related AEs has not been fully demonstrated, these events were shown to be associated with PFS 7 . The results of this study support this concept.…”

Section: Discussionsupporting

confidence: 63%

“…On the other hand, immune checkpoint inhibitors (ICI) are associated with characteristic adverse events (AEs), which are reported to occur in approximately 20% of patients, 6 and some patients do not achieve a therapeutic response because they stop treatment owing to AEs. However, some studies have shown that the appearance of AEs during treatment with an ICI is associated with their efficacy, 7 and the implications of AE for treatment efficacy are not yet fully understood. In this study, the safety of atezolizumab/bevacizumab combination therapy and the impact of AE on treatment efficacy were also examined.…”

Section: Introductionmentioning

confidence: 99%

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Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma

et al. 2023

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Background and Aim The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). Methods This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. Results The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin‐bilirubin (ALBI) grade and low level of des‐gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log‐rank tests with the Kaplan–Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. Conclusion Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma

et al. 2023

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“…A meta-analysis conducted by Tian et al 22 reported that the incidence of AEs in patients with HCC did not show a significant difference when compared with other tumor types. In a systematic meta-analytic review of ICI therapy for HCC, involving 6,472 patients across 47 studies, 83.4% experienced trAEs of any grade (95% confidence interval [CI], 77.0-89.1), with 33% (95% CI, 26.9-39.5) classified as grade 3 or higher.…”

Section: Incidence Of Iraes Analyzed In Meta-analysesmentioning

confidence: 98%

“…Among patients experiencing these AEs, 18.8% (95% CI, 13.2-25.2) received steroids, and 6.6% (95% CI, 4.6-9.0) discontinued treatment due to AEs. 22 …”

Section: Incidence Of Iraes Analyzed In Meta-analysesmentioning

confidence: 99%

“…Patients who experienced irAEs showed improved progression-free survival (PFS), but no significant difference in OS. 22 In a meta-analysis of 48 clinical trials involving 7,936 patients, the incidence of skin irAEs ( r =0.79; P <0.001), gastrointestinal irAEs ( r =0.56; P =0.006), and endocrine system irAEs ( r =0.44; P =0.05) was positively correlated with increased objective response rates (ORRs) following nivolumab treatment. Nevertheless, no analogous correlation was observed with liver, lung, and kidney irAEs.…”

Section: Association Between Iraes and Prognosismentioning

confidence: 99%

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Complications of immunotherapy in advanced hepatocellular carcinoma

Song,

Yoo,

Kim

et al. 2024

JLC

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Immune checkpoint inhibitors (ICIs) are highly effective in cancer treatment. However, the risks associated with the treatment must be carefully balanced against the therapeutic benefits. Immune-related adverse events (irAEs) are generally unpredictable and may persist over an extended period. In this review, we analyzed common irAEs reported in highly cited original articles and systematic reviews. The prevalent adverse reactions include fatigue, pyrexia, rash, pruritus, diarrhea, decreased appetite, nausea, abdominal pain, constipation, hepatitis, and hypothyroidism. Therefore, it is crucial to conduct evaluations not only of gastrointestinal organs but also of cardiac, neurologic, endocrine (including the frequently affected thyroid), and ophthalmic systems before commencing ICIs. This review further explores commonly reported types of irAEs, specific irAEs associated with each ICI agent, rare yet potentially fatal irAEs, and available treatment options for managing them.

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Immune-mediated liver injury from checkpoint inhibitors: mechanisms, clinical characteristics and management

Triantafyllou,

Gudd,

Possamai

2024

Nat Rev Gastroenterol Hepatol

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Adverse events of immune checkpoint inhibitors in hepatocellular carcinoma: a systemic review and meta-analysis

Cited by 8 publications

References 84 publications

Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma

Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma

Complications of immunotherapy in advanced hepatocellular carcinoma

Immune-mediated liver injury from checkpoint inhibitors: mechanisms, clinical characteristics and management

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