Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

Abstract

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.

Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis

“…Clinical trials conducted by Richard et al further confirmed that 15.2% of liver cancer patients who received the combination of bevacizumab and atezolizumab developed hypertension of grade 3 or 4 28 . In two clinical studies involving the combination of bevacizumab and atezolizumab, approximately 7% of participants experienced gastrointestinal bleeding 28,48 . Combination therapy was an independent risk factor for the development of hypertension and gastrointestinal bleeding, as confirmed by our study.…”

“…approximately 7% of participants experienced gastrointestinal bleeding. 28,48 Combination therapy was an independent risk factor for the development of hypertension and gastrointestinal bleeding, as confirmed by our study.…”

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

“…Several previous studies have reported that fatigue, liver injury, and m-ALBI grade are predictive factors for therapeutic effects or OS in patients treated with systemic therapy [ 18 , 27 , 28 ]. Fatigue can be detrimental to the patients’ quality of life [ 29 ], and preserved liver function is a favorable factor related to eligibility for post-treatment [ 30 ]. Sequential systemic therapy has recently been considered an effective strategy for the treatment of unresectable HCC.…”

Bevacizumab and Atezolizumab for Unresectable Hepatocellular Carcinoma: Real-world Data in Taiwan-Tainan Medical Oncology Group H01 Trial

“…Several studies have demonstrated that VEGF inhibition induces proteinuria in a dose-dependent manner. Higher dose of bevacizumab and longer treatment duration may contribute to higher incidence of proteinuria in Chinese subjects in IMbrave 150 trial (5). The optimal dose of bevacizumab remains a challenge because there is need to balance the efficacy of the atezolizumab/bevacizumab regimen and high incidence of proteinuria.…”