# Osimertinib-Induced Hepatitis Following Immunotherapy in a Patient with Lung Adenocarcinoma Harboring De Novo EGFR Exon 19 Deletion and T790M Mutations: A Case Report

## TL;DR

A patient with lung cancer experienced liver damage from a drug called osimertinib after immunotherapy, but successfully rechallenged the drug with steroid support.

## Contribution

This case report highlights the successful rechallenge of osimertinib after osimertinib-induced hepatitis, managed with steroids.

## Key findings

- Osimertinib caused severe hepatitis in a patient with EGFR-mutant lung cancer after immunotherapy.
- Rechallenging with osimertinib, alongside steroids, achieved disease control without recurrence of hepatitis.
- The case suggests osimertinib remains a viable treatment option after prior adverse events with proper management.

## Abstract

Background and Clinical Significance: Non-small-cell lung cancer (NSCLC) with EGFR mutations, particularly de novo compound mutations such as exon 19 deletions (Ex19del) with T790M substitutions, present a significant clinical challenge due to resistance to many treatments. While treating these patients, the administration of osimertinib, a third-generation EGFR inhibitor, after immunotherapy can lead to unique immune-related adverse events (irAEs), such as pneumonitis and, rarely, hepatitis. Case Presentation: A 36-year-old Filipino woman presented with metastatic NSCLC harboring de novo Ex19del and T790M mutations. Despite initial therapy with carboplatin and paclitaxel, followed by chemoimmunotherapy, the patient’s disease progressed. She subsequently developed severe hepatitis from osimertinib after her prior immunotherapy with pembrolizumab. After the hepatitis resolved with high-dose steroids, osimertinib was switched to afatinib, but her disease rapidly progressed with new metastases. A second attempt at osimertinib rechallenge, with concomitant prednisone, resulted in substantial disease control, including improved leptomeningeal disease (LMD) and no recurrence of hepatitis. Conclusions: This case underscores the feasibility of rechallenging with osimertinib in patients who experience adverse events such as hepatotoxicity, provided that appropriate management strategies, such as steroid therapy, are employed. The successful rechallenge in this case highlights the potential of osimertinib as a viable option in advanced EGFR-mutant NSCLC, even after prior treatment-related complications.