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.