Review article: Recommendations for detection, assessment and management of suspected drug-induced liver injury during clinical trials in oncology patients.

Background: Drug-induced liver injury (DILI) is a major concern for oncology drugs in clinical practice and under development. Monitoring cancer patients for hepatotoxicity is challenging as these patients may have abnormal liver tests pre-treatment or on-study for many reasons including liver injury due to past oncology treatments, hepatic metastases, medical co-morbidities such as heart failure, and concomitant medications. At present, there are no regulatory guidelines or position papers that systematically address best practices pertaining to DILI detection, assessment and management in oncology patients.

Aims: The goals of this review are (1) to examine and interpret the available evidence and (2) to make recommendations for detection, monitoring, adjudication, and management of suspected hepatocellular DILI during oncology clinical trials.

Methods: This manuscript was developed by the IQ Consortium (International Consortium for Innovation and Quality in pharmaceutical development) DILI Initiative that consists of members from 17 pharmaceutical companies, in collaboration with academic and regulatory DILI experts. The manuscript is based on extensive literature review, expert interpretation of the literature, and several rounds of consensus discussions.

Results: This review highlights recommendations for patient eligibility for clinical trials with or without primary/metastatic liver involvement, as well as changes in liver tests that should trigger increased monitoring and/or discontinuation of study drug. Guidance regarding causality assessment for suspected DILI events, rechallenge and dose-modification is provided.

Conclusions: This review brings together evidence-based recommendations and expert opinion to provide the first dedicated consensus for best practices in detection, assessment, and management of DILI in oncology clinical trials.