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Cardioncological Approach for Trastuzumab Therapy in Breast Cancer Patients With Cardiotoxicity: Impact on Adherence and Clinical Outcome.

ABSTRACT: Background:Treatment with Trastuzumab is associated with cardiotoxicity. If Trastuzumab could be administered in a safe manner to patients who develop a reduced left ventricular ejection fraction (EF) of < 50% remains poorly understood. Objective:To evaluate the impact of a cardioncological approach in terms of adherence and continuation of oncological therapy with Trastuzumab. Methods and Results:Internal databases of candidates for trastuzumab chemotherapy with evidence of cardiotoxicity according to echocardiographic criteria were retrospectively evaluated. Eighty-four female patients (age 51.7 years, 95% CI 49.5-53.8), were finally included. Patients were divided to receive a standard (n 27) or cardioncological (n 57) scheme. Baseline EF values were within normal limits (60.9, 95% CI 60 - 61.9%; p=0.5 between groups). The nadir of EF observed during trastuzumab therapy was more pronounced in the standard care group (40.6, 95% CI 37.3-43.9% vs. 46.3, 95% CI 44.3-48.3%; p=0.002). At re-challenge, after cardiotoxicity detection, all patients in the cardioncological arm resumed and completed trastuzumab therapy (p<0.0001). An overall reduction of EF was observed at the final evaluation (p <0.0001 vs. baseline). Cardioncological approach was the only independent determinant of ?EF from baseline to final evaluation (R20.12; p=0.004). We observed a total of 13 (15%) HF events, seven (26%) in the standard, and six (10%) in the cardioncological approach group (p =0.1). Patients in the cardioncological approach arm had a better outcome (Log Rank Chi-squared 4.89; p=0.02). Conclusions:A targeted cardioncological approach, in patients with evidence of cardiotoxicity during HER-2 inhibitor therapy, could favorably influence the oncological management of breast cancer patients, reducing the adverse cardiovascular impact of chemotherapy.

SUBMITTER: Fabiani I

PROVIDER: S-EPMC7417864 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cardioncological Approach for Trastuzumab Therapy in Breast Cancer Patients With Cardiotoxicity: Impact on Adherence and Clinical Outcome.

Fabiani Iacopo I Cipolla Carlo Maria CM Colombo Nicola N Cardinale Daniela D

Frontiers in pharmacology 20200804

<h4>Background</h4>Treatment with Trastuzumab is associated with cardiotoxicity. If Trastuzumab could be administered in a safe manner to patients who develop a reduced left ventricular ejection fraction (EF) of < 50% remains poorly understood.<h4>Objective</h4>To evaluate the impact of a cardioncological approach in terms of adherence and continuation of oncological therapy with Trastuzumab.<h4>Methods and results</h4>Internal databases of candidates for trastuzumab chemotherapy with evidence o ...[more]

PMID: 32848791

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Project description:BackgroundTrastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) experiencing treatment interruption or discontinuation.MethodsThe primary objective of the study was to evaluate disease-free survival (DFS) in non-metastatic, HER2-positive, female BC patients who experienced treatment interruption or early discontinuation of trastuzumab therapy. Clinical and histopathological data were collected on 400 patients at The Ohio State University, an NCI-designated comprehensive cancer center between January 2005 and December 2015. Treatment interruption was defined as any delay of ≥2 weeks during trastuzumab therapy, including permanent cessation prior to completing planned therapy. TIC was defined as LVEF < 50% or > 15 points decline from baseline as evaluated by 2D echocardiogram after initiation of (neo) adjuvant therapy. DFS was defined as the time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as the time from diagnosis to death or last known follow up. OS/DFS estimates were generated using Kaplan-Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHR) for OS/DFS.ResultsA total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) permanently discontinued trastuzumab prior to completing planned therapy. TIC was the most common reason for interruption (66 patients, 62%). The median duration of trastuzumab in patients with treatment interruption was 11.3 months (range: 0.5-16.9) with 24 (23%) patients receiving ≤6 months of therapy. This duration includes the time delay related to treatment interruption. Patients with any treatment interruption had worse DFS (aHR: 4.4, p = 0.001) and OS (aHR: 4.8, p < 0.001) after adjusting for age, stage, grade, ER, node status and TIC.ConclusionsTreatment interruption or early discontinuation of trastuzumab therapy in early HER2-positive BC, most often from TIC, is an independent prognostic marker for worse DFS and OS in operable HER2-positive BC. Future prospective studies should consider targeting at-risk populations and optimizing cardiac function to avoid interruption in trastuzumab therapy.

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).

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Cardioncological Approach for Trastuzumab Therapy in Breast Cancer Patients With Cardiotoxicity: Impact on Adherence and Clinical Outcome.

Publications

Cardioncological Approach for Trastuzumab Therapy in Breast Cancer Patients With Cardiotoxicity: Impact on Adherence and Clinical Outcome.

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