Corticosteroids for the management of immune-related adverse events in patients receiving checkpoint inhibitors.

INTRODUCTION: Due to enhanced T-cell activity, immune checkpoint inhibitors cause immune-related adverse effects. Corticosteroids are the mainstay of immune-related adverse effect management but the optimal strategy has not been determined, putting patients at risk for steroid-related adverse effects and potentially decreased efficacy of immunotherapy. This study aims to characterize the use of corticosteroids for the management of immune-related adverse effect. METHODS AND MATERIALS: A retrospective, single-center evaluation of patients receiving checkpoint inhibitors was conducted. The primary objective was to evaluate corticosteroid use for immune-related adverse effects, including starting dose, taper strategy, total duration, and resumption of immunotherapy. Secondary objective was to describe the incidence and significance of hyperglycemia. RESULTS: One hundred and three patients met inclusion criteria and experienced 123 immune-related adverse effects. Prednisone was used most commonly (67%) at an average starting dose of 0.88 mg/kg (range 0.07-17.0). On average, steroid tapers began 9.2 days after initiation (range 0-89) and were continued for a total of 84.2 days (range 3-693). In 21.1% of cases, checkpoint inhibitor therapy was not delayed and 68.6% resumed checkpoint inhibitors, while the patient was taking steroids (30.4 mg prednisone on average, range 5-80). On average, checkpoint inhibitor therapy was resumed 18.6 days after detection of immune-related adverse effect (range 0-150). Clinically relevant hyperglycemia occurred in 8.9%. CONCLUSION: Utilization of steroids for immune-related adverse effect at our institution is highly variable. The majority of patients received prolonged courses of steroids and resumed checkpoint inhibitor therapy with concomitant steroids above recommended doses. Additional monitoring for hyperglycemia and other steroid associated adverse effects should be considered.

Thromboembolic events in patients with colorectal cancer receiving the combination of bevacizumab-based chemotherapy and erythropoietin stimulating agents.

OBJECTIVE: To investigate whether the incidence of thromboembolic events (venous and arterial) increases when bevacizumab-based chemotherapy and erythropoietin stimulating agents (ESAs) are used in combination versus alone. METHODS: A retrospective, pilot study of 79 colorectal cancer patients treated with chemotherapy were divided into 3 groups: bevacizumab (n = 28), ESA (n = 21), and bevacizumab plus ESA (n = 28). The primary end point was the incidence of thromboembolic events. Secondary endpoints included median time-to-event; effect of anticoagulation; and association with concurrent chemotherapy, baseline risk factors, hemoglobin, and performance status. RESULTS: The incidence of thromboembolic events was 11% in the bevacizumab group, 23.8% in the ESA group, and 30% in the combination group (P = 0.194). The median time-to-event was 7.5, 3.5, and 2.5 months, respectively (P = 0.060). The 5 month difference in time-to-event between the bevacizumab group and combination group was significant (P = 0.045). When combining all patients, ESA treatment, prior venous thromboembolic event (VTE), obesity, cardiac disease, and use of exogenous hormones were strong predictors for thromboembolic events. Prior VTE was a strong predictor in those patients in the combination group. CONCLUSION: The incidence of thromboembolic events was increased with the combination of bevacizumab plus ESA compared with either agent alone with chemotherapy. Median time-to-event in the combination group was significantly shorter compared with the bevacizumab group. Prior VTE, cardiac disease, obesity, and exogenous hormone use should be taken in consideration when using the combination of bevacizumab and ESAs.

Sunitinib-related fulminant hepatic failure: case report and review of the literature.

Drug-induced hepatotoxicity is an infrequent but life-threatening complication. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma and gastrointestinal stromal tumor. However, results from preapproval clinical trials suggest an equivocal hepatic risk profile for sunitinib. We describe a 75-year-old woman with renal cell carcinoma who was admitted to the intensive care unit after experiencing fulminant hepatic failure during sunitinib therapy. The patient's hepatic and renal chemistries had been within normal limits throughout four previous cycles of sunitinib therapy spanning 9 months. After the fifth cycle, she complained of a 3-day history of severe diarrhea and dehydration. Her abnormal laboratory test results included the following: total bilirubin level 5.9 mg/dl, aspartate aminotransferase level 3872 U/L, alanine aminotransferase level 3332 U/L, ammonia level 897 microg/dl, and an international normalized ratio of 4.8. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between sunitinib and hepatotoxicity. Supportive care including aggressive intravenous hydration and reversal of coagulopathy was successful. The patient was discharged home on hospital day 7 without apparent longstanding sequelae. Clinicians should be aware of this possible adverse effect of sunitinib, and continued pharmacovigilance is imperative to accurately quantify the possible risk of sunitinib-related hepatotoxicity.