Gliflozines in active cancer patients with heart failure: final results on safety and effectiveness in the observational TOSCA trial

Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are currently a cornerstone for the treatment of heart failure (HF). However, there is a dearth of information regarding safety and efficacy in cancer patients because this category of patients has not been included in randomized controlled trials (RCTs). Purpose Aim of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. We now present the final results. Methods TOSCA was a multi-centre observational trial including adult active cancer patients (<3 years from diagnosis) with HF treated with SGLT2i. Patients were enrolled in either a prospective or a retrospective cohort. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness in terms of ejection fraction (EF) increase, New York Heart Association (NYHA) class change and HF-related cardiovascular events. Exploratory endpoints included drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in N-terminus-pro-brain natriuretic peptide (NT-proBNP). Results One-hundred and twenty-nine patients were enrolled (88 prospectively - 41 retrospectively) receiving either dapagliflozin (58%) or empagliflozin (42%) on top of guideline-recommended medical therapy for a median of 3 (range 3-25) months. Median age was 72 (range 44-92) years, male to female ratio was 51/49%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (73%) received an active treatment (mainly chemotherapy and target agents) while on SGLT2i. Prevalent etiology was drug-induced HF (35%) with HFrEF as the most frequent clinical presentation (44%). The incidence of urinary tract infections was 1.8%, with no cases of genital infections, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis or bone fractures. The mean overall ejection fraction increased (from 40.3% to 47.4%), and New York Heart Association (NYHA) class improved in 19% of cases. Rates of unplanned cardiology visits (0.9%), use of i.v. diuretics (0.9%), coronary angiography (4.5%), emergency access for HF (1.8%), and new HF episodes (3.6%) were extremely low. SGLT2i appeared effective in 34 cases of CTRCD. A reduction in mean NT-proBNP levels (2340±5042 vs 904±1725 pg/mL, p=0.055) was observed. No drug-drug interactions were reported. Conclusions SGLT2i confirmed their safety and effectiveness in active cancer patients with HF, with a potential cardioprotective effect. No new safety warnings were recorded.