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.

Liver toxicity in oncology trials and beyond: a simplified concept for management of hepatocellular drug-induced liver injury in patients with abnormal baseline liver tests.

Background: Management of side effects in clinical trials has to balance generation of meaningful data with risk for patients. A toxicity area requiring detailed management guidelines is drug-induced liver injury (DILI). In oncology trials, patients are often included despite baseline liver test abnormalities, for whom there is no consensus yet on levels of liver test changes that should trigger action, such as drug interruption or discontinuation.

A comprehensive analysis of liver safety across zibotentan oncology trials: knowledge of the past offers new perspectives on the present.

Background: Endothelin receptor antagonists (ERAs) are associated with liver injury. We used data from previous oncology clinical trials to determine the liver safety profile of zibotentan, which is currently in clinical development (in combination with dapagliflozin) for chronic kidney disease and cirrhosis.

Research Design And Methods: Six global, double-blinded, phase 2b and 3 clinical trials from the zibotentan oncology development program were pooled to analyze liver safety.

Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy.

Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents.

Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials.

Background: Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults.

Methods: We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2.