Subcutaneous Trastuzumab: What About Cardiac Toxicity? Real Life Study in a Moroccan Medical Oncology Department

Abstract

Introduction: Trastuzumab is a monoclonal antibody targeting the HER2 receptor. Initially, it was only administered intravenously. Since August 2013, the subcutaneous formulation has been introduced. The phase III HANNAH study demonstrated the non-inferiority of subcutaneous Trastuzumab compared to the IV in terms of efficacy and safety. At the medical oncology department of Souss Massa University Hospital, since 2019, Trastuzumab is only administered subcutaneously.

Objectives: The aim of our study is to report real-life data of cardiac toxicity of subcutaneous Trastuzumab.

Methods: We conducted a retrospective cohort study, performed at the Souss Massa University Hospital between January 2019 and December 2020. Our inclusion criteria were patients with HER2 positive localized breast cancer with good cardiac function. Cardiotoxicity was defined as a drop in LVEF below 50% or a 10-point drop from baseline EF or evidence of heart failure.

Results: Our study included 120 patients with a female predominance (99%). The average age was 49.81 years. Regarding cardiovascular risk factors, 1.66% of the patients were hypertensive, 5.83% were diabetic and 48.33% had a BMI>25. For tumour disease, the left breast was affected in 49.17% of the cases, 69.17% of the patients were hormone receptor positive. 4.16% were diagnosed with stage I, 47.5% with stage II and 48.33% with stage III. Therapeutically, 42.5% received neoadjuvant therapy. All patients underwent surgery but only 18.33% were able to benefit from conservative surgery. Sequential chemotherapy was used in all our patients except 5% who did not receive anthracyclines. Radiotherapy was indicated in 96.67% of cases. Initial LVEF was between 50 and 60% in 10%, between 60 and 70% in 62.5% and more than or equal to 70% in 27.5% of cases with an average of 66.28%. At the end of treatment, the average LVEF was 63% (49%-76%), a decrease in absolute value of 3.28% before and after using Trastuzumab. In 15 patients or 13.3%, subcutaneous trastuzumab had to be discontinued due to cardiotoxicity with a decrease in LVEF below 50% in 5 patients (4.16%), a decrease in LVEF of more than 10 points from baseline in 6 cases (5%) and more than 15 points in 3.33%. Subcutaneous injections were resumed in 11 patients (9.1%) after normalization of LVEF while it was permanently stopped in 4 patients (3.34%).

Conclusions: The use of subcutaneous Trastuzumab constitutes an indisputable progress in the treatment of breast cancer overexpressing HER2. Its cardiac safety in our real-life study is in line with that reported in the literature.