Can durvalumab be given to a patient with a history of gallbladder cancer who developed immune-mediated hepatitis after one cycle of chemotherapy?

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Last updated: January 22, 2026 • View editorial policy

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Durvalumab Should NOT Be Restarted After Immune-Mediated Hepatitis

Durvalumab must be permanently discontinued following immune-mediated hepatitis, regardless of whether it occurred after one cycle or multiple cycles. This is a critical safety issue that prioritizes patient survival and quality of life over potential oncologic benefit.

FDA-Mandated Permanent Discontinuation Criteria

The durvalumab FDA label explicitly requires permanent discontinuation for immune-mediated hepatitis meeting specific severity thresholds 1:

  • Grade 3 or 4 hepatitis (ALT/AST ≥5x ULN or bilirubin ≥2.5 mg/dL)
  • Grade 2 hepatitis that recurs after rechallenge
  • Any immune-mediated hepatitis requiring high-dose corticosteroids (≥40 mg prednisone equivalent daily) 1

Since your patient developed hepatitis severe enough to be clinically recognized after just one cycle, this almost certainly meets Grade 2 or higher criteria, mandating permanent discontinuation 1.

Clinical Evidence Supporting Non-Rechallenge

Hepatitis Incidence and Severity with Durvalumab

As monotherapy: Immune-mediated hepatitis occurred in 2.8% of patients, including fatal cases (0.2%), with Grade 3-4 events in 1.7% 1. All patients required systemic corticosteroids, and 2 patients needed additional immunosuppression with mycophenolate 1.

With tremelimumab (STRIDE regimen): The hepatitis rate increased to 7.5%, including fatal (0.8%) and Grade 3-4 (4.4%) events 1. All 29 patients required high-dose corticosteroids, and 8 required additional immunosuppressants 1.

Poor Outcomes Associated with Durvalumab-Related Liver Injury

A retrospective analysis of 112 durvalumab-treated patients found that liver injury during treatment was independently associated with mortality on multivariate analysis 2. Critically, only 27% of non-DILI liver injury cases (which includes immune-mediated hepatitis) had normalization of liver biochemistries, compared to 100% of pure DILI cases 2. This suggests immune-mediated hepatitis has a more persistent and potentially dangerous course than simple drug toxicity.

Alternative Treatment Options for Gallbladder Cancer

Since your patient has gallbladder cancer (a biliary tract cancer), evidence-based alternatives exist:

First-Line Options Without Durvalumab

Gemcitabine plus cisplatin plus pembrolizumab is now standard first-line therapy for advanced biliary tract cancer, achieving objective response rates of 40.9% in MSI-H/dMMR tumors 3. This avoids re-exposure to durvalumab while maintaining immunotherapy benefit.

Gemcitabine plus cisplatin alone remains an option if immunotherapy is contraindicated entirely, with established efficacy in biliary tract cancers 4, 5.

Why Rechallenge Is Contraindicated

The FDA label states that durvalumab should be permanently discontinued for Grade 3-4 immune-mediated hepatitis 1. Even if hepatitis resolved with corticosteroids, rechallenge risks:

  • Recurrent hepatitis (potentially more severe)
  • Fatal outcomes (documented in 0.2-0.8% depending on regimen) 1
  • Need for prolonged immunosuppression that may compromise cancer treatment efficacy 1

Critical Management Pitfalls to Avoid

Do not attempt rechallenge even if liver enzymes normalized with corticosteroids. The FDA label explicitly prohibits this for Grade 3-4 events 1.

Do not use the STRIDE regimen (durvalumab plus tremelimumab) as an alternative, as this has even higher hepatitis rates (7.5% vs 2.8%) and includes durvalumab 1.

Do not delay switching to alternative therapy. The association between liver injury during durvalumab treatment and increased mortality suggests that continuing the same agent (even after resolution) may worsen outcomes 2.

Recommended Treatment Algorithm

  1. Confirm permanent discontinuation of durvalumab per FDA labeling 1
  2. Ensure complete resolution of hepatitis with corticosteroid taper as needed 1
  3. Switch to gemcitabine/cisplatin/pembrolizumab if MSI-H/dMMR status confirmed 3
  4. Consider gemcitabine/cisplatin alone if all immunotherapy is contraindicated due to severe immune-related adverse event history 4, 5
  5. Monitor liver function closely with any subsequent systemic therapy 2

References

3
Guideline

Immunotherapy in Cholangiocarcinoma

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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