Safety assessment of trastuzumab diluted in 100 ml of saline in the treatment of HER2-positive breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11555-e11555
Author(s):  
Hajime Abe ◽  
Tsuyoshi Mori ◽  
Yuki Kawai ◽  
Kaori Tomida ◽  
Yoshihiro Kubota ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

e11555 Background: The infusion rate is considered to affect incidence and severity of infusion reaction (IR) caused by infusion of protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. We evaluated the safety of TRS intravenously administered over 30minutes with 100 ml saline to reduce burden of patients although safety of infusion with 250 ml saline is established. Methods: Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF) were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes diluted in 250 ml saline followed by 6mg/kg of TRS in 100 ml saline over 30 minutes in a three-week cycle. The primary endpoint of this study was the incidence of infusion reactions, and secondary endpoints were as follows: incidence of adverse events and effects on cardiac function. Results: Between June 2011 and June 2012, a total of 31 patients were recruited; 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range, 39 to 82). Hormone receptor was positive in 18 patients (58%). Previous treatment with anthracyclines was reported in seven patients and radiation therapy in fourteen patients. The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients and rash occurred in one patient at the first dose. However, no IR and adverse events were observed after reducing to 100 ml saline. The average LVEF measured every 3 months was between 62.3% and 64.8%. No significant decrease in LVEF was reported with the largest decrease of 8% in one patient at the 12th month on treatment. Conversely, brain natriuretic peptide levels tended to decrease as the number of received doses increased. None of the subgroup analysis (age groups, adjuvant vs. metastatic setting, previous anthracycline treatment, and previous radiotherapy) showed statistical significance. Conclusions: Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients is considered safe based on results from the study. The safe treatment with shorter infusion time has benefit for both healthcare professionals and patients. Clinical trial information: UMIN000006710.

scholarly journals Safety and Clinical Evaluation of Dual Inhibition with Pertuzumab and Trastuzumab Biosimilar SB3 in HER2-Positive Breast Cancer Patients

Breast Care ◽  
2021 ◽  
pp. 1-7
Author(s):  
Christoph Suppan ◽  
Daniel Steiner ◽  
Eva Valentina Klocker ◽  
Florian Posch ◽  
Elisabeth Henzinger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Safety And Efficacy ◽  
Her2 Positive Breast Cancer ◽  
Tumor Stages ◽  
Positive Breast Cancer

<b><i>Background:</i></b> The addition of trastuzumab to standard chemotherapy has improved survival in patients with HER2-positive breast cancer in neoadjuvant, adjuvant, and metastatic settings. In higher tumor stages, the addition of pertuzumab is now a standard of care and associated with a favorable toxicity profile. We evaluated the safety and efficacy of the trastuzumab biosimilar SB3 in combination with pertuzumab in HER2-positive breast cancer patients. <b><i>Methods:</i></b> Seventy-eight patients with HER2-positive breast cancer treated at the Division of Oncology at the Medical University of Graz were included. Summary measures are reported as medians (25th to 75th percentile) for continuous variables and as absolute frequencies (%) for count data. <b><i>Results:</i></b> Thirty-five patients received a median of 4 (3–7) cycles of trastuzumab biosimilar SB3 plus pertuzumab. All patients had a normal baseline left ventricular ejection fraction (LVEF; &#x3e;50%) prior to the initiation of SB3 plus pertuzumab treatment with a median LVEF of 60% (60–65). Twenty-one patients had a median absolute LVEF decline of 1% (–5 to 0). Two patients (5.7%) had a LVEF reduction ≤50%, but none ≥10%. There were no unexpected adverse events. Twenty-two of 35 patients (63%) were treated with trastuzumab biosimilar SB3 and pertuzumab in the neoadjuvant setting and 11 patients (50%) achieved a pathological complete response. The safety and the efficacy in this setting was comparable to the trastuzumab plus pertuzumab combination in neoadjuvantly treated matched samples. <b><i>Conclusion:</i></b> In this series of HER2-positive breast cancer patients, the combination of SB3 plus pertuzumab was consistent with the known safety and efficacy profile of trastuzumab and pertuzumab combination.

Objective response rate in a phase II multicenter trial of pertuzumab (P), a HER2 dimerization inhibiting monoclonal antibody, in combination with trastuzumab (T) in patients (pts) with HER2-positive metastatic breast cancer (MBC) which has progressed during treatment with T

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1004-1004 ◽  
Author(s):  
J. Baselga ◽  
D. Cameron ◽  
D. Miles ◽  
S. Verma ◽  
M. Climent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Objective Response ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Fixed Dose ◽  
Loading Dose ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

1004 Background: T and P bind to different epitopes on the extra cellular domain of HER2. Unlike T, P binds to the dimerization domain and blocks homo- and hetero-dimerization of HER2 with other HER kinase family members. Xenograft models support the hypothesis that the complementary mechanisms of action could result in augmented efficacy when T and P are combined. Methods: Two-stage design, criteria to proceed to the 2nd stage were: ≥ 2 partial responses (PR) or 1 PR and 12 stable disease (SDs) or 13 SDs. Eligibility included: measurable, centrally-tested HER2 positive breast cancer; up to 3 lines of prior chemotherapy plus T (including adjuvant chemotherapy plus T); disease progression during T as most recent treatment for metastatic disease; baseline left ventricular ejection fraction (LVEF) ≥ 55% and no decrease of LVEF to below 50% during prior T treatment. Consenting Pts received T i.v. weekly or every 3 weeks at 2 mg/kg or 6 mg/kg respectively (with re-loading dose if required) plus 420mg fixed dose of P i.v. every 3 weeks following loading dose 840mg. Study treatment was initiated within 9 weeks of the last dose of T given as most recent therapy. An independent data safety monitoring board has overseen the 1st stage safety data. Results: Recruitment into 1st stage is complete. The main adverse events were diarrhea (71%), fatigue (46%), nausea/vomiting (38%) and rash (25%). Most AE’s were mild to moderate (there was 1 case of Grade 3 diarrhea) and none was treatment-limiting. There were no clinical cardiac events, and central review revealed no case of fall in LVEF of ≥10% and to ≤50%. Response status: 5 confirmed PR (21%); 12 SD (50%). Responses have been observed in lymph node and liver metastases. Recruitment into the 2nd stage of the trial has commenced. Conclusions: The combination of the P and T is active and well tolerated in patients with pre-treated HER2 positive breast cancer which has progressed during treatment with T. No significant financial relationships to disclose.

Trastuzumab induced cardiotoxicity in HER2-positive metastatic esogastric cancers.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 152-152 ◽  
Author(s):  
Jerome Martin-Babau ◽  
Yves Eusen ◽  
Cedric Verveur ◽  
Fanny Trouboul ◽  
Caroline Cheneau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Cardiovascular Comorbidities

152 Background: Trastuzumab is widely used in Her2 positive metastatic esophageal and gastric cancers along with chemotherapy. Cardiotoxicity of trastuzumab has been described precisely in Her2 positive breast cancers and occurs with asymptomatic lowering of LVEF (Left Ventricular Ejection Fraction) in up to 10% of cases. Esogastric cancer patients are usually older and have more comorbidities than patients followed for breast cancer. Methods: This monocentric retrospective study measured the incidence of symptomatic and asymptomatic cardiotoxicity in patients treated for metastatic esogastric cancers and its potential impact regarding overall survival from October 2009 to September 2015. Patients should receive trastuzumab with chemotherapy during the period of study for treatment of Her2 positive metastatic esogastric cancer as first-line chemotherapy. Results: 27 patients received trastuzumab along with chemotherapy during the period of study. Median age was 62.3 years, sex ratio 21 M/6 W. The median number of cycles of trastuzumab was 5 cycles. The asymptomatic cardiotoxicity rate, defined by a drop of more than 10% of LVEF between the enrollment echocardiogram and the third month treatment echocardiogram, was of 22%. Symptomatic cardiotoxicity was observed in two patients (7.4%), with one cardiac failure and one myocardial infarction, with no associated death. Cardiovascular comorbidities and cardiac irradiation which is recurrent in this indication did not appear as a predictive factor of cardiotoxicity (p = 1). Overall survival of patients was not statistically modified by the occurring of cardiotoxicity even if we noted a trend to better outcome of the patients presenting an asymptomatic LVEF lowering. Conclusions: This study is to our knowledge the first to focus specifically on the cardiotoxicity of trastuzumab in esogastric metastatic Her2 positive cancer in the real world. These patients seem to be at a higher asymptomatic cardiac risk than breast cancer patients. However cardiovascular comorbidities didn’t appear as predictive factors of trastuzumab induced cardiotoxicity and should not prevent patient from benefiting of this treatment.

Safety and tolerability of subcutaneous trastuzumab and intravenous pertuzumab as adjuvant treatment for HER2 positive breast cancer: a pilot study

2021 ◽  
pp. postgradmedj-2021-140319
Author(s):  
Chi Yan Wong ◽  
Roland Leung ◽  
Gin Wai Kwok ◽  
Josephine Tsang ◽  
Bryan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pilot Study ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Secondary Outcome ◽  
Adjuvant Setting ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

BackgroundSubcutaneous (SC) trastuzumab is similar to intravenous trastuzumab in terms of pharmacokinetics, efficacy and tolerability. The use of dual anti-HER2 agents trastuzumab and pertuzumab has become the new standard for node-positive HER2-positive breast cancers at adjuvant setting, but the safety and tolerability of combining SC trastuzumab and intravenous pertuzumab is not well studied.MethodsThis was a prospective single-arm pilot study with locally advanced HER2-positive breast cancer who received adjuvant SC trastuzumab and intravenous pertuzumab after standard anti-HER2 treatment with chemotherapy. Primary outcomes included adverse events (AEs), severe AEs and cardiac AEs. Secondary outcome was invasive disease-free survival (iDFS).ResultsWith a median follow-up of 21.7 months, 20 patients were enrolled. One patient (5%) developed asymptomatic drop in left ventricular ejection fraction from 69% to 53%. Two patients (10%) developed grade 1 injection site reaction related to SC trastuzumab. There were no grade 2 or above AEs. All AEs were transient. No new AEs were observed. The 1-year iDFS was 90% (95% CI 0.656 to 0.974)ConclusionsCombination of SC trastuzumab and intravenous pertuzumab for HER2-positive breast cancer is a safe and well-tolerated option in adjuvant setting.

Trastuzumab-related subclinical cardiotoxicity in patients with early stage HER2-positive breast cancer: A retrospective single-center cohort study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10123-10123
Author(s):  
Olexiy Aseyev ◽  
Moira Rushton-Marovac ◽  
Freya L. Crawley ◽  
Christopher Johnson ◽  
Susan Faye Dent
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Early Stage ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Increased Risk ◽  
Positive Breast Cancer

10123 Background: Trastuzumab-based therapy (TT) is standard treatment for HER2-positive breast cancer (HBC). Subclinical cardiotoxicity (SCTx), defined as asymptomatic decline in left ventricular ejection fraction (LVEF) > 10% to < 50%, has been reported in up to 30 % of HBC patients (pts) receiving TT. Objectives included: determine prevalence of SCTx; associated risk factors (RF); and completion rates of TT in pts with HBC referred to a cardio-oncology clinic (COC). Methods: HBC patients receiving TT referred to the Ottawa Hospital COC were included. Demographics, TNM staging, performance status, stage, cardio-vascular (CV) RF (history of heart disease, hypertension, smoking, dyslipidemia, and diabetes), cardiac medications (CM) (ACE-inhibitors, beta-blockers), baseline LVEF, previous cancer therapy, baseline anthracycline exposure, previous radiation therapy (RT) (including mediastinal RT) were collected. LVEF was evaluated by ECHO or MUGA. Rate of successful completion of TT among pts with SCTx was determined. Risk ratio (RR) and logistic regression analysis was performed. Results: 240/408 BC pts referred to the COC (2008-2016) had HBC and 163/240 (68%) were referred with SCTx while on TT. 139/163 (85 %) pts with SCTx recovered after COC assessment: 77/163 (47%) pts were prescribed CMs. A significantly higher proportion of recovery was observed in pts who did not require CM (0.92 vs 0.78, p = 0.012; RR = 0.85, 95%CI:0.74-0.91). A total of 129/163 (79%) pts who experienced SCTx finished a full course of TT. Regression analysis found baseline LVEF, diabetes, and diastolic blood pressure as significant RFs for SCTx. There were no independent predictors for recovery after asymptomatic drop in LVEF while on TT. Diabetes (OR:2.97, 95%CI:1.3-6.8) and left chest wall RT (OR:2.4, 95%CI:1.1-5.6) significantly increased risk of permanent TT interruption in pts with asymptomatic drop in LVEF. Conclusions: The majority of HBC pts who experience SCTx can safely complete a full course of TT; many without use of CMs. While CV RFs were associated with increased risk of SCTx, this did not impact CV recovery after asymptomatic drops in LVEF.

Impact of obesity on safety outcomes and treatment modifications with ado-trastuzumab emtansine in breast cancer patients

2020 ◽  
pp. 107815522098264
Author(s):  
Anna Lee ◽  
Chris Larck ◽  
Donald C Moore
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Obese Patients ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Antibody Drug ◽  
Positive Breast Cancer

Introduction Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. The 2012 American Society of Clinical Oncology guidelines on chemotherapy dosing in obesity recommend using full weight-based cytotoxic chemotherapy doses to treat obese patients with cancer. These guidelines were published prior to the advent of anticancer antibody-drug conjugates. There is a need to investigate the safety of T-DM1 in obese patients. Methods This retrospective chart review included adult patients with breast cancer receiving T-DM1. The primary endpoint was a composite of the incidence of T-DM1 treatment modifications secondary to an adverse event. Secondary outcomes included the incidence of dose reductions, dose delays, treatment discontinuations, and adverse events. Results A total of 119 patients with HER2-positive breast cancer who received T-DM1 therapy were included in this study: 44 obese patients and 75 non-obese patients. The composite outcome of treatment modifications due to toxicity was significantly higher in obese patients compared to non-obese patients (45% vs 25%, p = 0.024). Treatment delays were significantly higher in obese patients (36% vs 16%, p = 0.011). All-grade adverse events with a higher incidence in obese patients included left ventricular ejection fraction decrease (11% vs 5%), bilirubin increase (32% vs 12%), thrombocytopenia (61% vs 55%), and peripheral neuropathy (34% vs 27%). Conclusions This study suggests obese patients receiving T-DM1 may require more treatment modifications secondary to adverse events compared to non-obese patients. Larger studies are needed to determine if obese patients are at higher risk for specific T-DM1-induced adverse events.

scholarly journals 2D-echocardiography vs cardiac MRI strain: a prospective cohort study in patients with HER2-positive breast cancer undergoing trastuzumab

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Nathalie I. Bouwer ◽  
Crista Liesting ◽  
Marcel J. M. Kofflard ◽  
Jasper J. Brugts ◽  
Marc C. J. Kock ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Global Longitudinal Strain ◽  
Radial Strain ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract Background We aimed to study the predictive value of early two-dimensional echocardiography (2DE) speckle tracking (ST) for left ventricular ejection fraction (LVEF) changes during trastuzumab treatment for HER2-positive breast cancer. Methods HER2-positive breast cancer patients receiving trastuzumab, with or without anthracycline, underwent 2DE-ST at baseline and after 3 and 6 months (m) trastuzumab. Cardiac magnetic resonance (CMR) imaging (with ST) was performed at baseline and 6 m. We studied the correlation between 2DE-ST- and CMR-derived global longitudinal strain (GLS) and global radial strain (GRS) measured at the same time. Additionally, we associated baseline and 3 m 2DE-ST measurements with later CMR-LVEF, and with cardiotoxicity, defined as CMR-LVEF < 45% and/or absolute decline > 10% during trastuzumab. Results Forty-seven patients were included. Median baseline LVEF was 60.4%. GLS measurements based on 2DE-ST and CMR showed weak correlation (Pearson’s r = 0.33; p = 0.041); GRS measurements were uncorrelated (r = 0.09; p = 0.979). 2DE-LVEF at baseline and 3 m, and 2DE-ST-GLS at 3 m were predictive of CMR-LVEF at 6 m. In contrast, the change in 2DE-ST-GLS at 3 m was predictive of the change in CMR-LVEF at 6 m, whereas the change in 2DE-LVEF was not. Importantly, the 11 patients who developed cardiotoxicity (28%) had larger 2DE-ST-GLS change at 3 m than those who did not (median 5.2%-points versus 1.7%-points; odds ratio for 1% difference change 1.81, 95% confidence interval 1.11–2.93; p = 0.016; explained variance 0.34). Conclusions Correlations between 2DE-ST and CMR-derived measurements are weak. Nevertheless, ST-measurements appeared useful to improve the performance of 2DE in predicting LVEF changes after 6 m of trastuzumab treatment.

scholarly journals P197 Assesment of cardiac function during trastuzumab therapy in HER2 positive breast cancer patients

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
I Krstic ◽  
M Deljanin Ilic ◽  
I Pejcic ◽  
S Vrbic ◽  
D Marinkovic
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Before And After ◽  
Echocardiographic Parameters ◽  
Positive Breast Cancer

Abstract Background Although trastuzumab has benefits in treatment of HER2 positive breast cancer, it also carries the risk of cardiotoxicity. It is very important to evaluate the cardiac status before and after therapy with trastuzumab, as well as monitoring of electrocardiografic and echocardiographic parameters. The aim of this study was to assess of cardiac function during trastuzumab therapy in HER2 positive breast cancer patients. Method Ninety six HER2 positive female breast cancer patients (mean age, 59.57 ± 9.6 years) were enrolled in the study. At the time, they were on sequential therapy with anthracyclines (IV to VI cycles) within the FAC regimen (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) on day 22, and after that trastuzumab therapy (6 mg/kg of body weight on day 21, for the period of one year). In all patients (pts) blood pressure (BP), heart rate (HR), electrocardiografic and echocardiographic parameters (left ventricular ejection fraction–LVEF(%); fractional shortening–FS(%); end-diastolic diameter–EDD(mm); left ventricular mass – LVM (g)) were assesed at the beginning and after the therapy with trastuzumab. Results There was no significant changes in arterial BP before and after trastuzumab in examined pts (systolic BP119.90 ± 16.04 mmHg vs 121.30 ± 13.06 mmHg; diastolic BP 75.89 ±7.25 mmHg vs 76.30 ± 7.65 mmHg) ns and HR (68.78 ± 7.69/min vs 67.92 ± 7.90/min) ns. All pts at the beginning and after the last therapy with trastuzumab on the electrocardiogram (ECG) were in sinus rhythm, one pts has LBBB and one RBBB. During therapy ectopic beats were registred in 11 pts, SVES in 7 (7.29%), VES in 4(4.16%). In the most of this patients with PSR in the middle of treatment period with trastuzumab sinus tachycardia was recorded as well. At the end of trastuzumab therapy in examined group LVEF was decreased by 1.73% (from 65.49 ± 5.82% to 63.76 ± 6.43%; p = 0.007), FS by 0.86% (from 36.18 ± 5.10% to 35.32 ± 4.91%; p = 0.123) ns, EDD increased by 1.26 mm (from 47.53 ± 4.48 mm to 48.80 ± 5.19 mm; p = 0.005) and LVM increased by 173.68 g (from 161.55 ± 43.76 g to171.15 ± 47.88 g; p = 0.031). Cardiotoxicity is registred in 4 (4.17%) patients, according to the criteria of EACVI and ASE. Results Tratsuzumab has not significant effect on BP and ECG changes.The rate of cardiotoxicity after trastuzumab therapy was low and was expressed through reduction of left ventricle ejection fraction, the increase in the end-diastolic diameter and the left ventricular mass.

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