Safety of Continuing Trastuzumab Despite Mild Cardiotoxicity

Leong, Darryl P.; Cosman, Tammy; Alhussein, Muhammad Mustafa; Tyagi, Nidhi Kumar; Karampatos, Sarah; Barron, Carly C.; Wright, Douglas; Tandon, Vikas; Magloire, Patrick; Joseph, Philip; Conen, David; Devereaux, P.J.; Ellis, Peter; Mukherjee, Som D.; Dhesy‐Thind, Sukhbinder

doi:10.1016/j.jaccao.2019.06.004

Cited by 58 publications

(47 citation statements)

References 19 publications

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“…The present findings show that even in Japan or Asia, where the incidence of heart disease is considered to be lower than that in the USA and Europe, 27-29 there is a significant number of types of asymptomatic LV dysfunction as well as a small but important number of types of symptomatic heart failure, which can potentially worsen the prognosis of cancer survivors. 30,31 The present results are consistent with recent trends in cardio-oncology research. Immediately after the introduction of molecular targeted drugs, cardiotoxicity was classified into type I (irreversible) and type II (reversible), 6 although increasing evidence suggests that this classification is incomplete and inaccurate.…”

Section: Subjectssupporting

confidence: 91%

Risk Profiling of Cancer Treatment-Related Cardiovascular Disorders in Breast Cancer Patients Who Received Adjuvant Chemotherapy With Trastuzumab

et al. 2020

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Background: The prognosis of cancer survivors has dramatically improved, but effective strategies for cancer treatment-related cardiovascular disorders (CTRCD) remain to be elucidated in the emerging field of cardio-oncology. In this study, we investigated risk factors for CTRCD in breast cancer patients treated with trastuzumab. Methods and Results: We performed a retrospective analysis of 141 consecutive women who received adjuvant trastuzumab, and underwent baseline (BL) and follow-up (FU) echocardiography at Juntendo University between April 2010 and December 2016. The major concomitant treatment was anthracyclines in 94% and radiotherapy in 53%. During the median treatment period of 11 months, there were 22 (15.6%) cardiology consultations, 3 (2.1%) treatment interruptions with irreversible CTRCD, and no deaths. Left ventricular ejection fraction (LVEF) was decreased from a median 67.5% (BL) to 63.4% (FU; P<0.0001), with reduced LVEF noted in 26.2% at FU<90%BL, in 13.5% at FU

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Section: Subjectssupporting

confidence: 91%

Risk Profiling of Cancer Treatment-Related Cardiovascular Disorders in Breast Cancer Patients Who Received Adjuvant Chemotherapy With Trastuzumab

et al. 2020

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Section: Resultsmentioning

confidence: 99%

Clinical Impact of Interruption in Adjuvant Trastuzumab Therapy in Patients with Operable HER-2 Positive Breast Cancer

Sardesai

Sukumar

Kassem

et al. 2020

Preprint

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Background: Trastuzumab-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. Methods: The 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. Results: A 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. Patients with any treatment interruption had worse DFS (aHR: 4.9, p<0.001) and OS (aHR: 2.4, p=0.058) after adjusting for age, stage, grade, ER, node status and TIC. Conclusions: Treatment 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.

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“…Trastuzumab can subsequently be restarted with resolution of cardiac dysfunction. However, since completion of this study, two = single arm prospective trials, SCHOLAR [ 39 ] and SAFE-HEaRt [ 22 ], have investigated the continuation HER2-targeted therapy while concomitantly starting cardioprotective therapy in patients who develop mildly reduced LVEF. Although larger and randomized trials are needed, both of these studies demonstrate safety data with lack of further deterioration in cardiac function in approximately 90% of cases.…”

Section: Discussionmentioning

confidence: 99%

“…The use of BB and ACEi prior to initiating anti-HER2 therapy needs to be carefully weighed against unintended consequences, such as rising health care costs, over-diagnosis or over-treatment associated with the increased use of cardiac surveillance and prophylactic therapy [ 43 ]. Close collaboration between oncologists and cardiologists is needed to guide personalized therapy for vulnerable patients [ 39 , 44 – 46 ]. Our institutional guidelines encourage referral to cardio-oncology for at–risk patients prior to initiating trastuzumab therapy and early intervention in patients who experience LVEF decline while on targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Clinical impact of interruption in adjuvant Trastuzumab therapy in patients with operable HER-2 positive breast cancer

et al. 2020

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Background Trastuzumab-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. Methods The 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. Results A 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. Conclusions Treatment 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.

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Safety of Continuing Trastuzumab Despite Mild Cardiotoxicity

Cited by 58 publications

References 19 publications

Risk Profiling of Cancer Treatment-Related Cardiovascular Disorders in Breast Cancer Patients Who Received Adjuvant Chemotherapy With Trastuzumab

Risk Profiling of Cancer Treatment-Related Cardiovascular Disorders in Breast Cancer Patients Who Received Adjuvant Chemotherapy With Trastuzumab

Clinical Impact of Interruption in Adjuvant Trastuzumab Therapy in Patients with Operable HER-2 Positive Breast Cancer

Clinical impact of interruption in adjuvant Trastuzumab therapy in patients with operable HER-2 positive breast cancer

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