Clinical significance of the management of adverse events and symptom cluster associated with advanced hepatocellular carcinoma after lenvatinib treatment

Objective To investigate the symptoms and symptom clusters in patients with advanced hepatocellular carcinoma ( HCC) receiving molecular-targeted therapy with lenvatinib, as well as the clinical significance of the management of symptoms and symptom clusters in reducing lenvatinib-related grade 3 or above adverse events ( AEs) and AEs leading to treatment termination. Methods A total of 98 patients with advanced HCC who were treated with lenvatinib in The Fifth Medical Center of Chinese PLA General Hospital from May 2017 to December 2018 were enrolled. The AEs associated with lenvatinib were observed according to National Cancer Institute Common Toxicity Criteria, and the primary endpoint was the number of cases with a reduced dose or interruption of lenvatinib or treatment termination due to lenvatinib-related AEs after the management of symptoms or symptom clusters. Results All 98 patients completed the whole procedure.As for the lenvatinib-related AEs with an incidence rate of > 20%, hypertension had the highest incidence rate of 42. 9%, followed by diarrhea ( 33. 6%) , hepatic encephalopathy ( 30. 6%) , anorexia ( 30. 6%) , proteinuria ( 25. 5%) , fatigue ( 25. 5%) , hand-foot syndrome ( 22. 4%) , hoarseness ( 20. 4%) , and weight loss ( 20. 4%) . The incidence rate of grade 3 or 4 AEs was 55. 1% ( 54/98) ; the most common grade 3 AEs were hypertension ( 8. 2%) and hepatic encephalopathy ( 6. 1%) , and grade 4 AE was observed in 1 patient ( 1%) . The most common symptom clusters included hypertensive proteinuria ( 56. 1%) , digestive tract syndrome ( 50%) , and pain syndrome ( 36. 7%) . Among the 98 patients, 41 ( 41. 8%) had a reduced dose or interruption of lenvatinib due to lenvatinib-related AEs after the management of symptoms and symptom clusters and 4 ( 4. 1%) experienced treatment termination, which was lower than the percentages of 52. 9% and 8. 8% in the REFLECT study. Conclusion Hypertension and diarrhea are common AEs associated with lenvatinib. Hypertensive proteinuria, digestive tract syndrome, and pain syndrome are the main symptom clusters. Symptom cluster management is an effective means to reduce lenvatinib-related AEs leading to treatment termination.