Dataset Information

Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab.

ABSTRACT:

Introduction

Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity.

Materials and methods

We performed a retrospective cohort study of patients referred to the cardio-oncology service at McMaster University from 2016 to 2021 for LV dysfunction following trastuzumab administration.

Results

Fifty-one patients underwent permissive cardiotoxicity. The median (25th-75th percentile) follow-up time from cardiotoxicity onset was 3 years (1.3-4 years). Forty-seven (92%) patients completed trastuzumab; 3 (6%) developed severe LV dysfunction or clinical heart failure (HF) while on trastuzumab and prematurely discontinued therapy. One discontinued trastuzumab by patient choice. At final follow-up after therapy completion, 7 (14%) patients still had mild cardiotoxicity, including 2 who had clinical heart failure and stopped trastuzumab early. Among those with recovered LV function, 50% had normalized LVEF or GLS by 6 and 3 months, respectively, after initial cardiotoxicity. There was no difference in characteristics between those who did or did not recover their LV function.

Conclusions

Among patients exposed to permissive trastuzumab cardiotoxicity for HER2-positive breast cancer, 6% were unable to complete planned trastuzumab due to severe LV dysfunction or clinical HF. Although most patients recover their LV function after trastuzumab discontinuation or completion, 14% still have persistent cardiotoxicity by 3-year follow-up.

SUBMITTER: Zhou S

PROVIDER: S-EPMC10485282 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab.

Zhou Shijie S Cirne Filipe F Chow Justin J Zereshkian Arman A Bordeleau Louise L Dhesy-Thind Sukhbinder S Ellis Peter M PM Mukherjee Som D SD Aghel Nazanin N Leong Darryl P DP

The oncologist 20230901 9

<h4>Introduction</h4>Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity.<h4>Materials and methods</h4>We performed a retr ...[more]

PMID: 37094996

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Project description:BackgroundTrastuzumab is highly effective for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer but is associated with a decline in left ventricular ejection fraction.ObjectivesThe purpose of this study was to determine whether angiotensin-converting enzyme inhibitors or beta-blockers reduce the rate of trastuzumab-induced cardiotoxicity (left ventricular ejection fraction decrease >10%, or >5% if below 50%) and limit treatment interruptions.MethodsIn this double-blind, multicenter, placebo-controlled trial, cardiotoxicity and treatment interruptions in patients with HER2-positive breast cancer treated with trastuzumab for 12 months were evaluated over a 2-year period. Patients were stratified by anthracycline use and then randomized to receive lisinopril, carvedilol, or placebo.ResultsThe study included 468 women, age 51 ± 10.7 years. For the entire cohort, cardiotoxicity was comparable in the 3 arms and occurred in 32% of patients on placebo, 29% on carvedilol, and 30% on lisinopril. For patients receiving anthracyclines, the event rates were higher in the placebo group (47%) than in the lisinopril (37%) and the carvedilol (31%) groups. Cardiotoxicity-free survival was longer on both carvedilol (hazard ratio: 0.49; 95% confidence interval: 0.27 to 0.89; p = 0.009) and lisinopril (hazard ratio: 0.53; 95% confidence interval: 0.30 to 0.94; p = 0.015) than on placebo. In the whole cohort, as well as in the anthracycline arm, patients on active therapy with either angiotensin-converting enzyme inhibitor or beta-blockers experienced fewer interruptions in trastuzumab than those on placebo.ConclusionsIn patients with HER2-positive breast cancer treated with trastuzumab, both lisinopril and carvedilol prevented cardiotoxicity in patients receiving anthracyclines. For such patients, lisinopril or carvedilol should be considered to minimize interruptions of trastuzumab. (Lisinopril or Coreg CR in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab; NCT01009918).

Project description:BackgroundWhile trastuzumab has been shown to improve disease-free and overall survival in patients with HER2-positive breast cancer, it may also cause trastuzumab-induced cardiotoxicity (TIC). Although racial and ethnic minorities are at higher risk for cardiovascular disease (CVD) compared to non-Hispanic Whites (NHW), limited data exists on TIC incidence in diverse multi-ethnic populations. Our objective was to assess racial and ethnic differences in TIC and left ventricular ejection fraction (LVEF) recovery among patients with HER2-positive breast cancer.MethodsWe conducted a retrospective cohort study including patients diagnosed with stage I-III HER2-positive breast cancer between 2007 and 2022 who had received adjuvant trastuzumab. We analyzed associations between sociodemographic factors, tumor characteristics, treatment regimens, and CVD risk factors with the primary outcomes of TIC and LVEF recovery, using multivariable logistic regression models. TIC was defined as > 10% decrease in LVEF to an overall LVEF < 50%; LVEF recovery as a return to a LVEF > 50%.ResultsAmong 496 evaluable patients, median age was 53 years (IQR: 45.0-62.0) with 36.6% NHW, 15.8% non-Hispanic Black (NHB), 27.8% Hispanic, and 19.8% Other. Fifty-three (10.6%) patients developed TIC, half of whom experienced LVEF recovery. Compared to NHW, NHB had a higher rate of TIC (9.3% vs. 17.7%, respectively) and lower rate of LVEF recovery (70.6% vs. 21.4%, respectively), however, race/ethnicity was not a significant predictor of TIC after adjusting for confounders. Increasing age, lower baseline LVEF, anthracycline use, and presence of hypertension or coronary artery disease were significantly associated with TIC in multivariable analysis.ConclusionsTIC was more common among NHB compared to NHW, however, Black race was not consistently associated with TIC after adjustment for CVD risk factors. This suggests that CVD comorbidities (e.g., hypertension) that more frequently affect racial and ethnic minorities and are modifiable may explain differences in TIC incidence and recovery.

Project description:PurposeThe KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2-positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE.MethodsPatients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery).ResultsOf patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment.ConclusionCompared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.

Dataset Information

Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab.

Introduction

Materials and methods

Results

Conclusions

Publications

Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab.

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