Pembrolizumab plus anthracyclines in triple-negative breast cancer: prospective evaluation of early cardiac safety
TL;DR
Biomarker elevations were common but rarely translated into functional cardiac impairment, supporting the short-term cardiac safety of pembrolizumab when managed within a structured cardio-oncology surveillance program.
Abstract
Pembrolizumab combined with anthracycline-based chemotherapy has become standard neoadjuvant treatment for early triple-negative breast cancer (TNBC). However, concerns persist regarding potential additive cardiotoxicity. Prospective real-world data on early cardiac safety of this combination remain limited. To prospectively evaluate early cancer therapy–related cardiac dysfunction (CTRCD) in patients with early TNBC treated according to the KEYNOTE-522 protocol, using the 2022 ESC cardio-oncology definitions. Consecutive patients with early TNBC receiving neoadjuvant pembrolizumab combined with taxane–carboplatin followed by anthracycline-based chemotherapy were prospectively enrolled. Cardiac monitoring included serial transthoracic echocardiography with left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), electrocardiogram (ECG), and serial measurements of high-sensitivity cardiac troponin I (hs-cTnI) and NT-proBNP prior to the start of anthracyclines administration, at the completion of NACT and at 3 months and 12 months after the end of anthracycline therapy. CTRCD was defined according to ESC criteria. Fifty-eight patients were included (mean age 54 years). One patient died from cancer progression and was censored from follow-up. Overall, 32 of 57 patients (56.1%) fulfilled the primary endpoint, predominantly driven by biomarker-defined cardiotoxicity. Two patients (3.5%) experienced symptomatic heart failure during the initial phase of treatment with paclitaxel, carboplatin, and pembrolizumab and therefore did not receive anthracyclines. Moderate asymptomatic CTRCD occurred in 2 patients (3.5%) with concomitant LVEF and GLS decline, while 4 patients (7.0%) developed mild CTRCD with isolated GLS reduction. No patient developed symptomatic heart failure during or after anthracycline therapy. Significant hs-cTnI elevation was observed in 17.5% of patients, with 80% occurring during anthracycline administration. NT-proBNP elevations were frequent, resulting in a 49.1% incidence of mild cardiotoxicity according to HFA-ICOS criteria. No cases of myocarditis, acute coronary syndrome, arrhythmia, or atrioventricular block were identified. In this prospective real-world cohort, with near-complete echocardiographic follow-up (97.8% of planned echocardiographic assessments in patients treated with anthracyclines), the addition of pembrolizumab to anthracycline-based neoadjuvant chemotherapy was not associated with increased early cardiotoxicity. Biomarker elevations were common but rarely translated into functional cardiac impairment, supporting the short-term cardiac safety of pembrolizumab when managed within a structured cardio-oncology surveillance program.