Background: Alectinib is approved for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring ALK rearrangements. Although generally well tolerated, alectinib can cause serious or life-threatening side effects.
Case Presentation: Here, we report a case of a patient with NSCLC with an EML4-ALK  fusion and was treated with alectinib but who developed grade 4 hyperbilirubinemia after five months on therapy. Alectinib was discontinued, and an artificial liver support system (ALSS) was used with an impressive decline in bilirubin levels. After two months drug-free, the patient experienced disease progression. Ensartinib was initiated as second-line treatment with a best response of stable disease after three months of therapy with no evidence of hyperbilirubinemia.
Conclusion: This is the first report of ensartinib treatment after alectinib-induced hyperbilirubinemia which was successfully relieved by ALSS treatment and targeted drug cessation.
Keywords: ensartinib, alectinib, hyperbilirubinemia, NSCLC, ALK