Pembrolizumab plus anthracyclines in triple-negative breast cancer: prospective evaluation of early cardiac safety
A Besnard, A Patsouris, L Biere, E MervoyerAbstract
Background
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.
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.