Rationale: Hepatotoxicity is a well-known adverse effect of vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), usually employed for the treatment of metastatic renal cell carcinoma (mRCC). Immune checkpoint inhibitors (ICIs) have been shown to improve survival in specific patients with mRCC, but concerns have arisen over their safety profile, particularly as regards the risk of liver damage in those patients receiving TKIs sequentially or concurrently with these new drugs. Here, we report three cases of hepatitis presentation in patients receiving TKIs after ICIs that should potentially be considered in current clinical practice, where a combination of these hepatotoxic drugs is becoming increasingly used.
Patients concerns: All three patients were receiving TKIs therapy and presented with nonspecific clinical deterioration and liver enzyme elevation in different time frames according to the start of treatment. All were previously treated with ICIs.
Diagnoses: After performing imaging techniques and complementary laboratory tests for the differential diagnosis of hepatic injury, the diagnosis of potentially TKI-induced hepatitis was assumed in all these cases. Hepatic biopsy was performed only in the first case in order to confirm the diagnosis.
Interventions: Potential toxic drugs were interrupted and steroids course with slow reduction regimen was administered in all these cases because of the previous use of ICIs.
Outcomes: The patients described improved with this conservative treatment without complications during the following weeks. Only one case presented a new episode of mild hepatic alteration while on treatment with following treatment.
Lessons: Taking into account this new therapeutic context, stricter monitoring for potentially increased/altered adverse events should be indicated. Adequate patient selection and consideration of the safety profile of the different drugs used could help to optimize treatment in the near future.