4.3 Immunotherapy related cardiotoxicity
Screening, prediction and risk stratification of trastuzumab-induced cardiotoxicity should incorporate cardiac imaging assessment, biochemical markers and prior anthracycline use (44). Initiation of effective prophylactic therapy, such as β-blockers and ACEIs/ARBs, appeared to mitigate risk of trastuzumab-induced cardiotoxicity in patients receiving HER2-directed therapy (44). The SAFE-HEaRt trail enrolled evaluable thirty breast cancer subjects with lessened LVEF within 40-49% took over ACEIs and β-blockers treatment, of whom 29 patients finished the designed HER2-targeed treatment (45). ACEIs and β-blockers showed beneficial performance on preventing cardiotoxicity in evaluable 6, 542 women newly diagnosed with breast cancer undergoing trastuzumab/anthracycline treatment (46). However, sometimes the performance of β-blockers and ACEIs were not satisfactory. A patient with HER2-positive breast cancer experienced worsening cardiotoxicity-related HFrEF after suboptimal responses to traditional guideline-recommended medications for heart failure (47). The patient’s heart function greatly improved after the initiation of sacubitril/valsartan for four weeks, contributing to subsequent trastuzumab targeted therapy (47) (Table 1 ).
Sacubitril/valsartanl regimen started as first-line treatment in a patient with relapsing leukaemia and HFrEF caused by previously rituximab therapy (48). Primitive sacubitril/valsartanl regimen was well tolerable and created a durable improvement of symptoms, LVEF and NT-proBNP concentration, contributing to un-delayed cancer treatment (48) (Table 1 ). With the development of cancer immunotherapy, ICIs-induced cardiotoxicity has gained increasing attention. A patient with urothelial carcinoma experienced ICIs-induced myocarditis after suboptimal responses to hormone therapy. The patient’s cardiotoxicity-related HFrEF greatly improved after the initiation of sacubitril/valsartan for eight weeks combined with Tozizumab and gamma globulin therapy (49) (Table 1 ).
Summary and future perspectives
Chemotherapy-induced cardiotoxicity represents a potentially life threatening complication of anti-tumor treatment in cardio-oncology setting. Project proposals have been made to prevent and cure this complication, particularly through management with neuroendocrine inhibitors. Sacubitril/valsartan currently stood currently for an innovator in the clinical setting of therapy for HFrEF. Current evidences suggest that despite derived from small observational studies, sacubitril/valsartan appears to the intriguing role in treatment of cardiotoxicity-related HFrEF. Sacubitril/valsartan improved the clinical symptomatic status, exercise tolerance, LV functional and structural parameters and cardiac biochemical marker in patients with CTRCD (49).
Although the demonstration of a beneficial effect of sacubitril/valsartan on CTRCD is promising, the conclusions of these small observational studies remain only speculative in cancer survivors. Therefore, the performance of sacubitril/valsartan in patients with CTRCD requires further investigation. Further larger cohort studies and randomized clinical trials are needed to determine the performance of ARNI for the prevention and treatment of CTRCD. A randomized, double blind, multi-center, clinical trial has been designed to assess whether sacubitril/valsartan could prevent cardiotoxicity in early breast cancer patients receiving adjuvant or neo-adjuvant treatment regimens containing anthracyclines (50) (Table 1 ).
The landscape of CTRCD is still comparably new and with rapid developments in the cardio-oncology setting. Prevention and treatment of CTRCD is required to admit of a comprehensive all-round tumor treatment. A focus on available sacubitril/valsartan regimen should be implemented to get this goal.