Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer

Q: What are the key findings of this study?

Trastuzumab-related cardiotoxicity occurred in 16.6% of early breast cancer patients overall and increased significantly with baseline HFA-ICOS risk category (14.0% low vs 30.3% high/very high; p=0.002).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: HER2-positive early breast cancer (n=931). Intervention: High/very high HFA-ICOS cardiovascular risk score on curative trastuzumab vs. Low HFA-ICOS cardiovascular risk score on curative trastuzumab. Primary outcome: Overall cardiotoxicity (composite of LVEF decline ≥10%, LVEF decline below 50%, symptomatic congestive heart failure, cardiac death, or trastuzumab discontinuation due to cardiac toxicity) (p=0.002).

Q: What does this research mean for the field?

Cardiotoxicity occurs in approximately 16.6% of real-world patients receiving curative trastuzumab for HER2-positive early breast cancer and is significantly higher among patients classified as high or very high risk by the HFA-ICOS risk stratification tool. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Nicolò Matteo Luca Battisti; María Sol Andrés; Karla A. Lee; Sivatharshini Ramalingam; Tamsin Nash; Stephanie Mappouridou; Nishanthi Senthivel; Kalaprapa Asavisanu; Mariam Obeid; Elli‐Sophia Tripodaki; Vasileios Angelis; Emily Fleming; E. Goode; Stuart David Rosen; Mark J Allen; Susannah Jane Stanway; Alexander Richard Lyon; Alistair E. Ring

doi:10.1007/s10549-021-06192-w

April 5, 2021Breast Cancer Research and TreatmentOpen Access

Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer

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Key result

High baseline HFA-ICOS risk linked to ~2.2-fold higher trastuzumab-related cardiotoxicity.

P=0.002
n=931

Why the study?

Cardiotoxicity remains a concern in patients with HER2-positive early breast cancer receiving curative trastuzumab, and data on its incidence and risk prediction outside of clinical trials are limited.

Key Points

To evaluate real-world cardiotoxicity rates and assess the performance of the HFA-ICOS risk stratification tool in patients receiving curative trastuzumab for HER2-positive early breast cancer.
Retrospective single-center study of 931 patients treated with curative trastuzumab between 2011 and 2018 at The Royal Marsden NHS Foundation Trust.
Cardiotoxicity was monitored via left ventricular ejection fraction (LVEF) decline, congestive heart failure (CHF), treatment discontinuation, and cardiac death.
Baseline cardiovascular risk was categorized by the HFA-ICOS tool into low (401 [43.1%]), medium (454 [48.8%]), high (70 [7.5%]), and very high (6 [0.6%]).
Overall cardiotoxicity occurred in 155 patients (16.6%), comprising LVEF decline ≥10% in 141 (15.1%), LVEF <50% in 55 (5.9%), NYHA class II CHF in 42 (4.5%), NYHA class III-IV CHF in 5 (0.5%), and discontinuation due to cardiac reasons in 35 (3.8%), with 0 cardiac deaths.
Cardiotoxicity rates increased with baseline HFA-ICOS risk categories: 14.0% in low risk, 16.7% in medium risk, and 30.3% in high/very high risk (p=0.002).
For predicting any cardiac event (high/very high versus low/medium risk), the HFA-ICOS tool showed a sensitivity of 14.8%, specificity of 93.2%, PPV of 30.3%, NPV of 84.6%, and an AUC of 0.56.

Study Design

Type

Cohort (n=931)

Multicenter

No

PICO

P

Population

931 predominantly female patients (mean age 54.3 years, range 24-83) with curable HER2-positive early breast cancer treated with neoadjuvant or adjuvant trastuzumab at a single UK center between 2011 and 2018.

E

Exposure / Comparator

High/very high HFA-ICOS cardiovascular risk score on curative trastuzumab vs Low HFA-ICOS cardiovascular risk score on curative trastuzumab

O

Primary Outcome

Overall cardiotoxicity (composite of LVEF decline ≥10%, LVEF decline below 50%, symptomatic congestive heart failure, cardiac death, or trastuzumab discontinuation due to cardiac toxicity), p=0.002

Main Result

Absolute Event Rate: 30.3% vs 14%

p-value: p=0.002

Limitations

Retrospective single-center study design subject to selection bias
Cardiac biomarkers such as troponin and natriuretic peptides were not routinely measured and could not be included in the risk model
Baseline cardiac assessments used either MUGA scans or echocardiograms to measure LVEF, potentially introducing measurement bias
Global longitudinal strain (GLS) on speckle tracking echocardiography became standard practice only in 2016 and was not captured
Exclusion of patients who did not complete their full course of trastuzumab at the institution may have contributed to selection bias

Implication

May guide tailored monitoring intensity during trastuzumab; leaves open prospective validation of HFA-ICOS discrimination.

Abstract

PurposeTrastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.MethodsPatients receiving curative trastuzumab between 2011-2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used.Results931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%).Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline≥10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed.Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p=0.002). ConclusionsCardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity

Discussion

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Cite This Study

Battisti et al. (2021) conducted a cohort in HER2-positive early breast cancer (n=931). High/very high HFA-ICOS cardiovascular risk score on curative trastuzumab vs. Low HFA-ICOS cardiovascular risk score on curative trastuzumab was evaluated on Overall cardiotoxicity (composite of LVEF decline ≥10%, LVEF decline below 50%, symptomatic congestive heart failure, cardiac death, or trastuzumab discontinuation due to cardiac toxicity) (p=0.002). Trastuzumab-related cardiotoxicity occurred in 16.6% of early breast cancer patients overall and increased significantly with baseline HFA-ICOS risk category (14.0% low vs 30.3% high/very high; p=0.002).

synapsesocial.com/papers/6ae7aa3bccd8c1dc4d4f89ac https://doi.org/10.1007/s10549-021-06192-w

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Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer

Key Points

Study Design

PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Incidence of cardiotoxicity and validation of the Heart Failure Association-International Cardio-Oncology Society risk stratification tool in patients treated with trastuzumab for HER2-positive early breast cancer

Key Points

Study Design

PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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