What are the potential side effects of atezolizumab (atezolizumab) and bevac barg (bevacizumab) combination therapy in an adult cancer patient?

Atezolizumab Plus Bevacizumab Side Effects

The combination of atezolizumab plus bevacizumab causes hypertension (30%), fatigue (20%), proteinuria (20%), elevated AST (20%), and pruritus (20%) as the most common adverse events, with upper gastrointestinal bleeding occurring in 7% of patients despite variceal screening. 1

Most Common Adverse Events

Bevacizumab-Related Toxicities

• Hypertension is the most frequent adverse event, occurring in approximately 30% of patients 1, 2
• Proteinuria develops in 20% of patients, with grade 3-4 proteinuria in 7% 3
• Upper gastrointestinal bleeding occurs in 7% of patients despite mandatory endoscopic screening and variceal treatment 1
• Hemorrhage of any type is reported in 25% of patients receiving atezolizumab-bevacizumab versus 17% with sorafenib 2

Atezolizumab-Related Toxicities

• Fatigue/asthenia affects 20% of patients 2
• Pruritus occurs in approximately 20% of patients 1
• Hypothyroidism develops in 11% of patients 1
• Pneumonitis occurs in 1.2% of patients 1

Hepatic and Laboratory Abnormalities

• Elevated AST occurs in 20% of patients 1
• Abnormal hepatic function can be treatment-related and fatal 3

Serious Adverse Events

Grade 3-4 Toxicities

• Hypertension is the most common grade 3-4 adverse event, occurring in 13% of patients 3
• Grade 3-4 proteinuria occurs in 7% of patients 3
• Serious adverse events occur in 38% of patients receiving the combination versus 31% with sorafenib 1

Treatment-Related Deaths

• Treatment-related grade 5 adverse events occur in 4.6% of patients 1
• Documented causes of treatment-related death include abnormal hepatic function, hepatic cirrhosis, and pneumonitis 3

Critical Pre-Treatment Requirements

Mandatory Variceal Screening

• All patients must undergo upper endoscopy within 6 months prior to treatment initiation due to bleeding risk 1
• Patients with portal hypertension require adequately treated varices before starting therapy 1
• This screening requirement stems from prior phase 2 studies showing increased gastrointestinal bleeding with bevacizumab in HCC 1

Specific Exclusion Criteria from Clinical Trials

The IMbrave150 trial excluded patients with: 1

• Autoimmune diseases (except autoimmune hypothyroidism on replacement, type 1 diabetes on insulin, and skin-only autoimmune conditions)
• Current immunosuppressive medication use
• History of organ or allogeneic stem cell transplantation
• Inadequately controlled hypertension
• Gastroesophageal varices incompletely treated or at high risk for bleeding
• Current therapeutic use of antiplatelet agents, anticoagulants, or thrombolytics

Treatment Discontinuation

Discontinuation Rates

• Treatment discontinuation due to adverse events occurs more frequently with atezolizumab-bevacizumab than sorafenib, though specific rates vary 1
• Atezolizumab discontinuation occurs in 5.3% of patients 4
• Bevacizumab discontinuation occurs in 7.9% of patients 4

Management of Immune-Related Adverse Events

• 29% of patients require immunomodulatory agents (high-dose glucocorticoids ≥40 mg prednisone daily or equivalent) to manage select treatment-related adverse events 1
• Despite this requirement, quality of life remains superior to sorafenib throughout treatment 1

Comparative Toxicity Profile

Versus Sorafenib

• Diarrhea is significantly less common with atezolizumab-bevacizumab (19%) compared to sorafenib (49%) 1
• Anorexia is less frequent with atezolizumab-bevacizumab (18%) versus sorafenib (24%) 1
• Palmar-plantar erythrodysesthesia occurs with sorafenib but not with atezolizumab-bevacizumab 2

Special Population Considerations

Child-Pugh B Patients

• Atezolizumab plus bevacizumab has no efficacy or safety data for Child-Pugh B or C patients and is not recommended 5
• Real-world data shows low efficacy and manageable but concerning toxicity in Child-Pugh B patients 6
• In patients with compromised liver function (Child B and C), treatment should be well considered before administration due to low efficacy 6

Asian Populations

• Asian patients may find it difficult to continue the recommended dose due to adverse events, making dose reduction at appropriate timing very important 1
• Autoimmune events with atezolizumab are reported to be manageable in Asian populations 1

Critical Clinical Pitfalls

Bleeding Risk Management

• The 7% incidence of upper gastrointestinal bleeding persists despite mandatory endoscopic screening and variceal treatment 1
• Patients at high risk for bleeding must be evaluated and managed before initiating therapy 1

Monitoring Requirements

• Blood pressure monitoring is essential given the 30% incidence of hypertension 1
• Proteinuria monitoring is required given the 20% incidence 3
• Thyroid function monitoring is needed given the 11% incidence of hypothyroidism 1