Prospective cardiovascular surveillance of immune checkpoint inhibitor-based combination therapy in patients with early-stage, triple-negative breast cancer.

Abstract

2607 Background: Both pembrolizumab and anthracyclines (AC) can cause adverse cardiovascular events; combination therapy is approved for high-risk, early-stage, triple-negative breast cancer (TNBC) and may further increase real-world cardiovascular risk. Cardiac surveillance with serial troponin measurements has been advocated in this population, though evidence supporting this approach is lacking. Methods: High-sensitivity troponin I (hs-TnI) was prospectively measured at baseline and with each treatment cycle in cancer patients receiving immune checkpoint inhibitors (ICI) at a single center as part of an institutional surveillance protocol for ICI-related adverse events from 2020-2022. Acute cardiac injury was defined as ≥1 abnormal hs-TnI value (>17ng/dL in women and >35ng/dL in men) with normal baseline hs-TnI, or at least 20% increase in hs-TnI from abnormal baseline. The incidence of acute cardiac injury and all-cause mortality were compared between patients receiving ICI in combination with AC versus ICI without AC. Results: Among 215 patients treated with ICI with baseline and ≥1 follow-up hs-TnI value, 28 patients (13%) received ICI with AC, all of whom were women with early-stage TNBC receiving pembrolizumab and AC-containing chemotherapy. 187 patients (87%) received ICI without AC for other oncological indications. Patients receiving ICI with AC were younger and more likely to be female than patients receiving ICI without AC (p<0.001) with lower rates of smoking, hypertension, and diabetes (p<0.04). Acute cardiac injury was observed in 33 patients, 21% of those receiving ICI with AC (N=6) and 14% of those receiving ICI without AC (N=27; p=0.34). Among these 33 patients, 2 patients were treated for ICI-associated myocarditis (1 receiving ICI with AC, 1 receiving ICI without AC); 67% of those receiving ICI with AC (N=4) were continued on ICI while only 30% of those receiving ICI without AC (N=8) were continued on ICI (p=0.16). The rate of all-cause mortality was significantly lower in patients receiving ICI with AC (0%) as compared to patients receiving ICI without AC (40%, p<0.001). Conclusions: Among women with early stage TNBC receiving pembrolizumab with AC, the rate of acute cardiac injury by surveillance troponin measurements was numerically but not statistically higher than for patients receiving ICI without AC for other oncological indications, though the rate of all-cause mortality was significantly lower. These findings suggest that surveillance troponin monitoring may have less clinical utility among women with early-stage TNBC receiving ICI-based combination therapy as compared to other patient populations receiving ICI. Further study is needed to understand the mechanistic and prognostic significance of acute cardiac injury in patients with TNBC receiving ICI-based combination chemotherapy.