Is it safe to proceed with Avastin (bevacizumab) and Tecentriq (atezolizumab) today in a patient with elevated bilirubin (bili) and alkaline phosphatase (alk phos) levels, and mild hypocalcemia?

Safety Assessment for Avastin and Tecentriq Administration with Abnormal Liver Function Tests

Based on the patient's laboratory values (bilirubin 1.80, alkaline phosphatase 250, anion gap 4, calcium 7.8), it is not recommended to proceed with Avastin (bevacizumab) and Tecentriq (atezolizumab) today due to the elevated liver function tests that may indicate underlying hepatic dysfunction.

Analysis of Laboratory Values

The patient presents with:

• Bilirubin: 1.80 mg/dL (elevated)
• Alkaline phosphatase (ALP): 250 U/L (elevated)
• Anion gap: 4 (low)
• Calcium: 7.8 mg/dL (hypocalcemia)

Liver Function Assessment

1. Elevated Bilirubin (1.80 mg/dL):

   • According to consensus guidelines for clinical trials, total bilirubin >1.0× ULN is an exclusion criterion for patients with liver disease 1
   • Elevated bilirubin may indicate impaired liver function which can affect drug metabolism

2. Elevated Alkaline Phosphatase (250 U/L):

   • Elevated ALP is a common laboratory abnormality seen in patients receiving Tecentriq 2
   • However, baseline elevation may indicate underlying cholestatic liver disease or biliary obstruction
   • The FDA label for Tecentriq notes that liver function laboratory abnormalities including increased transaminases, bilirubin, or alkaline phosphatase led to treatment interruption in 8% of patients 2

Safety Considerations for Immunotherapy Administration

Tecentriq (Atezolizumab) Considerations:

• The FDA label for Tecentriq indicates that adverse reactions leading to discontinuation included increased transaminases or bilirubin (1.2%) 2
• Immune-related adverse reactions requiring systemic corticosteroid therapy occurred in 12% of patients receiving Tecentriq with bevacizumab 2
• Liver function laboratory abnormalities are among the most common reasons for treatment interruption 2

Avastin (Bevacizumab) Considerations:

• When combined with Tecentriq, liver function abnormalities are a significant concern
• The combination therapy is primarily studied in patients with Child-Pugh class A liver function 1
• The ASCO guideline recommends caution in patients with more advanced liver disease due to increased risk of bleeding complications 1

Management Recommendations

Immediate Actions:

1. Postpone treatment today until further evaluation of liver function

2. Investigate the cause of elevated liver enzymes:

   • Consider GGT to confirm hepatobiliary origin of elevated ALP 3
   • Rule out biliary obstruction with imaging (ultrasound or MRI/MRCP) 3
   • Evaluate for viral hepatitis, autoimmune hepatitis, or drug-induced liver injury 3

3. Address hypocalcemia (calcium 7.8 mg/dL) before considering treatment

Monitoring and Follow-up:

• Repeat liver function tests in 2-3 days 1
• For patients with elevated baseline ALT ≥1.5× ULN, an ALT elevation >2× baseline warrants close observation and monitoring 1

Treatment Resumption Criteria:

• Consider resuming treatment when:
  • Bilirubin returns to normal range
  • ALP shows significant improvement
  • Calcium is corrected to normal range
  • Any underlying cause of liver dysfunction is addressed

Evidence-Based Rationale

The IMbrave150 trial, which established atezolizumab-bevacizumab as first-line treatment for hepatocellular carcinoma, included primarily Child-Pugh class A patients 1, 4. The trial showed that liver function laboratory abnormalities were among the most common reasons for treatment interruption 2.

Real-world studies have shown that while atezolizumab plus bevacizumab can be effective, special attention should be paid to liver function 5. Elevated bilirubin can also interfere with accurate measurement of ALP, potentially complicating assessment of liver function 6.

Conclusion

The patient's elevated bilirubin and alkaline phosphatase, along with hypocalcemia, present safety concerns for administering Avastin and Tecentriq today. Further evaluation of liver function and correction of electrolyte abnormalities should be completed before proceeding with treatment.