SAFE-HEaRt: A pilot study assessing the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and reduced left ventricular function.

Lynce, Filipa; Barac, Ana; Geng, Xue; Dang, Chau T.; Yu, Anthony F.; Smith, Karen L.; Gallagher, Christopher; Pohlmann, Paula Raffin; Nunes, Raquel; Herbolsheimer, Pia; Warren, Robert; Srichai, Monvadi B.; Hofmeyer, M.; Cunningham, A.; Timothee, Patricia; Asch, Federico M.; Shajahan-Haq, Ayesha N.; Tan, Ming; Isaacs, Claudine; Swain, Sandra M.

doi:10.1200/jco.2018.36.15_suppl.1038

Cited by 9 publications

(7 citation statements)

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“…92,93 The severe toxicity incidence rate is about 1% as per recent evidence, among which cardiac toxicity has been the most predominant limiting factor for the use of trastuzumab. 94,95 Earlier published adjuvant clinical trials report grade 3–4 cardiac toxicity (1–4%) in trastuzumab-treated patients. Fortunately, such cardiac dysfunction is reversible through the removal of dose accumulative effects.…”

Section: Anti-her2-targeted Agentsmentioning

confidence: 99%

“…96 Currently, there are no confirmed biomarkers that can precisely predict the occurrence of cardiac toxicity after trastuzumab use. 95 However, prior or concomitant use of anthracycline and trastuzumab agents may result in a high risk of dose-dependent irreversible cardiac damage in HER2-positive patients. Finally, strategies for preventing left ventricular ejection fraction (LVEF) deterioration have been explored, which include new combinations with other cytotoxic agents (vinorelbine, taxanes, and platinum) to avoid anthracycline use.…”

Section: Anti-her2-targeted Agentsmentioning

confidence: 99%

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Targeted therapeutic options and future perspectives for HER2-positive breast cancer

Wang

2019

Sig Transduct Target Ther

310

241

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Over the past 2 decades, there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) are commonly recommended anti-HER2 target agents by the U.S. Food and Drug Administration. This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices. In this article, we present the data on anti-HER2 clinical research of neoadjuvant, adjuvant, and metastatic studies from the past 2 decades. We also highlight some of the promising strategies that should be critically considered. Lastly, this review lists some of the ongoing clinical trials, findings of which may soon be available.

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Section: Anti-her2-targeted Agentsmentioning

confidence: 99%

Section: Anti-her2-targeted Agentsmentioning

confidence: 99%

Targeted therapeutic options and future perspectives for HER2-positive breast cancer

Wang

2019

Sig Transduct Target Ther

310

241

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“…Finally, the SAFE-HEaRT study prospectively evaluated the cardiac safety of HER2-directed treatment in 31 asymptomatic patients with left-ventricular ejection fraction (LVEF) ≥40% <50% under optimal cardioprotective treatment including β‑blockers and ACE inhibitors [16]. A cardiac event (defined as symptomatic heart failure or an LVEF drop of ≥10% from baseline and/or ≤35%) was observed in three subjects.…”

Section: Clinical Practicementioning

confidence: 99%

ASCO 2018: highlights in HER2-positive metastatic breast cancer

Bartsch

Bergen

2018

memo

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SummaryAt the 2018 ASCO Annual Meeting, data from several interesting studies in HER2-positive metastatic breast cancer were presented. While not immediately practice changing, these trials indicate the future directions of drug development in this field. Early phase studies with novel antibody-drug conjugates (ADCs) such as trastuzumab-deruxtecan and trastuzumab-duocarmazine suggest relevant clinical activity of these drugs in pretreated patients; in addition, these ADCs may offer activity in low HER2-expressing tumours as well. ZW25, a bispecific HER2-directed antibody targeting the extracellular domains 2 and 4, showed excellent tolerability and considerable single-agent activity. A combination of T‑DM1 with the tyrosine-kinase inhibitor neratinib yielded high response rates, while a study of trastuzumab plus durvalumab reported disappointing results. Although formally negative, overall survival data from the PHEREXA trial suggest clinical activity of dual HER2-inhibition with trastuzumab and pertuzumab in patients with prior trastuzumab treatment for advanced disease. A combined analysis of two tucatinib studies showed that systemic therapy is active when continued in case of isolated central nervous system progression and stable extracranial disease after local therapy of brain metastases; finally, a small prospective observation in asymptomatic patients with reduced left ventricular ejection fraction suggests that anti-HER2 treatment may be reasonably safe in this population.

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“…Yet, others have shown the feasibility of T in the context of low baseline LVEF, thus further encouraging anti-HER2 treatment despite adverse cardiac scenarios with careful cardiac assessment and optimal adjustment of cardioprotective medications. 39 , 40 …”

Section: Discussionmentioning

confidence: 99%

Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial

et al. 2020

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Background Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting. Methods This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm. Results With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68–1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4–11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55% (vs > 64%, OR 3.1 [95% CI 1.54–6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25–2.75]), BMI > 30 kg/m 2 (vs < 25 mg/kg 2 , OR 2.21 [95% CI 1.40–3.49]), cumulative dose of doxorubicin ≥240 mg/m 2 (OR 1.36 [95% CI 1.01–1.82]) and of epirubicin≥ 480 mg/m 2 (OR 2.33 [95% CI 1.55–3.51]). Conclusions Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial. Trial registration number ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006–000562–36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2–06 /EGF106708/N063D.

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SAFE-HEaRt: A pilot study assessing the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and reduced left ventricular function.

Cited by 9 publications

References 0 publications

Targeted therapeutic options and future perspectives for HER2-positive breast cancer

Targeted therapeutic options and future perspectives for HER2-positive breast cancer

ASCO 2018: highlights in HER2-positive metastatic breast cancer

Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial

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