Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians

Abstract

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Osimertinib‐related liver injury with successful osimertinib rechallenge: A case report

“…Houron et al have published a comprehensive literature review on multikinase inhibitor‐related hepatotoxicity. The authors reported that the latency is usually between one week to two months, and the TKI‐related liver toxicity is often hepatocellular and less frequently mixed 9 . When it comes to osimertinib, the latency is 15 days to one month 3–5 .…”

“…The DILI network categorizes liver injury into 18 histological patterns 10–12 . Previous reports of liver biopsy pathology of EGFR TKI (gefitinib, erlotinib) showed active hepatitis with portal inflammation and bridging fibrosis 9 . In the case reported by Gonzalez et al, the pathology of liver biopsy revealed pericentral confluent necrosis which is classified as zone necrosis in the DILI network system and the portal tracts showed mild nonspecific chronic inflammation 5 .…”

“…The authors reported that the latency is usually between one week to two months, and the TKI-related liver toxicity is often hepatocellular and less frequently mixed. 9 When it comes to osimertinib, the latency is 15 days to one month. [3][4][5] In our case, the latency was nine months and Rvalue was 0.57 (hepatocellular [R > 5], choleostatic [R < 2], or mixed DILI [2 < R < 5]), suggesting cholestatic DILI.…”

Drug-Induced Liver Injury: Highlights and Controversies in the Recent Literature

“…Miller et al [99] Rate of ILICI in combination therapy of an anti-CTLA-4 and anti-PD-1 (9.2%) compared with monotherapy with an anti-CTLA-4 (1.7%) or anti-PD-1 (1.1%) multi-kinase inhibitors used in clinical practice [128]. They noted that any aminotransferase elevation was exceedingly common, and that grade 3-4 hepatitis, defined as aminotransferase levels > 5× ULN, has been detected in 0-29% of patients treated with tyrosine kinase inhibitors in clinical trials.…”

“…The authors note that while most cases are asymptomatic and reversible, there is a 0.2-0.5% prevalence of acute liver failure related to afatinib, ceritinib, crizotinib, and regorafenib. Therefore, they recommend routine laboratory monitoring of ALT during treatment with tyrosine kinase inhibitors [128]. Liver test monitoring as part of a Risk Evaluation and Mitigation Strategy has been recommended for pexidartinib, a newly approved colony-stimulating factor-1 receptor inhibitor used in the management of patients with tenosynovial giant cell tumors [129].…”