Background: SGLT2 inhibitors have dramatically improved the outcome of heart failure patients with both preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction. Cancer patients have been excluded (or not enrolled) from pivotal trials so data on safety in such population are lacking. We aimed to collect evidence on safety and activity of empagliflozin and dapagliflozin in active cancer patients.
Study design: TOSCA is a retrospective/prospective multicentre observational trial now enrolling cancer patients receiving SGLT2i for both HFpEF, HFmrEF and HFrEF. Inclusion criteria included active cancer (histologically confirmed current cancer or history of cancer in previous 3 yrs), heart failure (HF) and SGLT2i therapy for HF. Exclusion criteria were age <18yrs, non-melanoma skin cancer and localised cervical cancer undergone radical treatment. Primary objective is assessing the safety of SGLT2i in active cancer patients expressed as percentage of toxicity (in particular hypoglycaemia, genital and urinary infections, acute renal failure, fractures, diabetic ketoacidosis and thromboembolic events) compared to side effects reported in phase III RCTs. Secondary objective is assessing the efficacy (change in EF, NYHA class variation, hospital/ER admissions for HF, need for diuretics) and exploratory objectives are time course variation of cardiac biomarkers, efficacy in the treatment of cardiac toxicity and drug-drug interactions with anticancer or supportive care drugs. A three months minimum follow-up will be required for every enrolled patient. Planned sample size is 80 patients (to be increased to a maximum of 200 cases) equally distributed between the two study cohorts. Relevance of expected results: SGLT2i are one of the pillars of HF treatment; the proof of safety (and activity) in active cancer patients could allow a wider cancer population to benefit of their efficacy in reducing cardiovascular mortality and could provide the rational basis for RCTs testing their role as cardio-protective strategy.