Safety of trastuzumab, alone or in combination, in elderly patients with HER2-positive breast cancer: A 5-year case series.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11056-e11056 ◽  
Author(s):  
Vincenzo Adamo ◽  
Giuseppina R. R. Ricciardi ◽  
Barbara Adamo ◽  
Giuseppa Ferraro ◽  
Tindara Franchina ◽  
...  

e11056 Background: Breast cancer (BC) is frequent in the elderly and is burdened by high recurrence and death rates, due mostly to undertreatment. Trastuzumab (T), in combination with chemotherapy (CT) or hormonotherapy (HT), is a well-established treatment strategy for early and advanced HER2-positive (HER2+) breast cancer, but has been poorly studied in the elderly setting due to its infrequency. The aim of our study is to assess the safety of T in elderly patients with HER2+ BC. Methods: Between 2005 and 2010, consecutive HER2+ breast cancer patients of ≥70 years of age referred to two oncology centers and that received T-based therapy were retrospectively reviewed. All patients were treated according to multidimensional geriatric assessment (MGA) and clinical criteria. Results: Of 59 patients, 51 were evaluable with a mean age of 76 years (range 70-86). Trastuzumab was well tolerated overall. Median left ventricular ejection function (LVEF) at baseline was 61% and at the end of treatment was 55%. The most relevant adverse events consisted of only one case (2%) of symptomatic congestive heart failure, which required treatment withdrawal and six (12%) asymptomatic decreases of LVEF (3 pts >15% and 3 pts >10% versus baseline). Mild to moderate hypersensitivity reactions associated with T-containing infusions occurred in 3 patients (5.8%). Hypertension, obesity and previous anthracycline-based treatment and combination with CTs gave a trend towards a higher incidence of toxic events. Previous radiotherapy, concurrent HT and the different T schedules did not influence toxicity. Conclusions: Our data shows a good trastuzumab safety profile in non-frail women age 70 and older. These favourable findings may be related to the limited number of anthracycline pre-treatments, a substantial patient selection by MGA and close cardiologic monitoring. [Table: see text]

Breast Care ◽  
2021 ◽  
pp. 1-7
Author(s):  
Christoph Suppan ◽  
Daniel Steiner ◽  
Eva Valentina Klocker ◽  
Florian Posch ◽  
Elisabeth Henzinger ◽  
...  

<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.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 632-632 ◽  
Author(s):  
M. Spielmann ◽  
H. Roché ◽  
T. Delozier ◽  
G. Romieu ◽  
H. Bourgeois ◽  
...  

632 Background: Following the BCIRG 001, PACS 01 and HERA trials, this randomised, multicentre, open-label, Phase III trial was designed to demonstrate the benefit of concomitant docetaxel and epirubicin versus anthracyclines, and evaluate the use of sequential trastuzumab. Methods: Patients (pts) with localised, resectable, unilateral breast cancer who met the following criteria were eligible: age <65 years, ≥1 positive node, M0, adequate heart and organ functions. Pts were randomised to receive either 6 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC100: F and C, 500 mg/m2, E 100 mg/m2) (Arm A) or epirubicin-docetaxel (ET75: E 75 mg/m2, T 75 mg/m2) (Arm B). Primary prophylaxis with G-CSF was not planned. Radiotherapy was mandatory after conservative surgery and tamoxifen was required in pts with hormone receptor-positive tumours. Pts with HER2-positive disease were then further randomised to observation only or to 1 year of trastuzumab monotherapy (6 mg/kg iv every 3 weeks). In HER2-positive pts receiving trastuzumab, left ventricular ejection fraction (LVEF) was determined at Cycles 2, 4, 8, 13, 18 and after 2 years. Otherwise, LVEF was determined at baseline and at 1 year post-surgery. Results: Of the 3010 pts recruited (2622 evaluable for safety to date), 1518 received FEC100 and 1492 received ET75 after the first randomisation. Haematologic toxicity was the most frequent toxicity in both arms. Grade 3–4 toxicities were similar for Arms A and B, except febrile neutropenia (10.3% and 31.4%, respectively) and nausea/vomiting (13.2% and 7.5%, respectively). Grade 2 clinical cardiac toxicity (decreased LVEF) was observed in 4 pts in Arm A and 5 in Arm B, with median LVEF scores of 63% in both arms at the end of chemotherapy. HER2-positive pts (n=500) were then randomised to either receive trastuzumab (n=259) or observation only (n=241). Conclusions: These preliminary safety data indicate that FEC100 and ET75 were both well tolerated, with acceptable cardiac safety values. The trial is ongoing and further analysis regarding the use of trastuzumab in this setting will be presented. [Table: see text]


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 282-282 ◽  
Author(s):  
L. Militello ◽  
P. Carli ◽  
S. Spazzapan ◽  
C. Lestuzzi ◽  
G. Miolo ◽  
...  

282 Background: T is a mainstay in adjuvant therapy for HER2+ breast cancer (BC) patients (pts). Safety and efficacy of T in elderly patients are largely unknown. In HERA trial, NSABP B-31, NCCTG N9831 only 16% of pts were older than 60 years. Risk factors for T related cardiotoxicity are age (>50 y/o), hypertension, baseline LVEF (left ventricular ejection fraction <55%), previous antracycline therapy and BMI. Methods: Charts of pts >65 y/o with early HER2+ BC treated with T as adjuvant or neoadjuvant therapy at our institution were retrospectively reviewed. Primary endpoint was the evaluation of T cardiac toxicity and safety. Results: 22 elderly out of 172 pts (12%) were identified: 19 pts were treated only with surgery and adjuvant chemotherapy with concomitant or sequential T, 3 more pts also received neoadjuvant chemotherapy concomitant with T. According to Balducci’s criteria, fit, vulnerable and frail pts were 20, 2, 0 respectively. Median age was 69 y/o (range 65-76). Hormonal status was negative in 10/22 (45%). 21/22 were histologic grade 3. Median follow-up was 33 months. Baseline comorbidities were the following: hypertension (G2-3) in 17 pts, diabetes mellitus in 1, supra/infraventricular arrhythmia (G1-2) in 3 and 1 pts. Antracyclines were administered in 16 pts (liposomal-doxorubicin in 5 pts), a sequential taxane-regimen was used in 3 more pts. Neoadjuvant weekly Paclitaxel and concomitant T was used in 3 pts. Median basal LVEF was 65% (range 59-74%). 2 pts developed an asymptomatic 10% LVEF drop from baseline (left ventricular systolic dysfunction G1) during T treatment. Known cardiac risk factors were hypertension in 1 pt and previous antracycline based chemotherapy in both. They recovered within 9 months. One minor adverse event was atrial fibrillation (G2) during T treatment. Conclusions: T was well tolerated in elderly pts. More data are needed in order to understand the correlations between T related toxicity and cardiovascular risk factors. Long term safety of T treatment should verify the reversibility of cardiac T related toxicity on elderly pts.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 152-152 ◽  
Author(s):  
Jerome Martin-Babau ◽  
Yves Eusen ◽  
Cedric Verveur ◽  
Fanny Trouboul ◽  
Caroline Cheneau ◽  
...  

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11555-e11555
Author(s):  
Hajime Abe ◽  
Tsuyoshi Mori ◽  
Yuki Kawai ◽  
Kaori Tomida ◽  
Yoshihiro Kubota ◽  
...  

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.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12059-e12059
Author(s):  
Oluchi Oke ◽  
Carla L. Warneke ◽  
Mariana Chavez-Mac Gregor ◽  
Andrea Milbourne ◽  
Jennifer Keating Litton

e12059 Background: Overexpression of HER2 is associated with aggressive breast cancers. In non-pregnant HER2+ breast cancer patients, anti-HER2 therapy is usually initiated after surgery or in the neoadjuvant setting. However, for pregnant HER2+ breast cancer patients, anti-HER2 therapy must be delayed until after delivery due to fetal toxicity. We describe here the outcomes of pregnant patients with HER2+ breast cancer at a single center. Methods: Twenty-three pregnant HER2+ breast cancer patients were treated between November 1989 to October 2016. Median age at diagnosis was 31.8. (Table 1) We report Kaplan-Meier estimates of OS from diagnosis and PFS from surgery. The effect of time from diagnosis to anti-HER2 therapy (TTH) on OS and PFS from HER2 therapy initiation was assessed using Cox proportional hazards regression models. Results: Seventeen patients received anti-HER2 therapy after delivery, 6 did not – 4 were treated prior to the use of HER2 therapies, and 2 were lost to follow-up. Median TTH was 181 days. All but 3 patients started HER2 treatment within 2 months of delivery. Twenty-one received anthracycline-based chemotherapy during pregnancy. Three patients have died, with all 3 receiving HER2 therapy, but one only at relapse due to diagnosis before routine trastuzumab use. Median follow-up was 3.4 years (range 0.2-16.2 years), and 5-year OS was 80% (95%CI 41-95%). Five patients progressed. Median PFS was 3.1 years (range 0.3-14.2 years), and 5-year PFS was 75% (95%CI 46-90%). Delay of initiation of HER-2 therapy did not appear to be associated with OS or PFS from date of HER-2 therapy initiation (both n = 17, HR 1.01, 95%CI 0.97-1.06, P= 0.52). Conclusions: In this small case series, we did not detect adverse outcomes associated with delaying initiation of anti-HER2 therapy in pregnant patients with HER2+ breast cancer. Larger series are needed to further evaluate this concern. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1033-1033 ◽  
Author(s):  
Isabel Blancas ◽  
Celia Gómez ◽  
Francisco Javier Martín-Pérez ◽  
Jose Manuel Garrido ◽  
Fernando Rodríguez-Serrano

1033 Background: The introduction of trastuzumab in the treatment scheme of the HER2 BC patients has improved the evolution of the disease. Nevertheless, some of this patients develop cardiotoxicity. We studied some of our population of HER2 positive BC patients treated with trastuzumab trying to find predictors for developing cardiotoxicity, specifically the association of the HER2 Ile655Val A˃G polymorphism with trastuzumab-induced cardiotoxicity and with survival and some biochemical and clinical features. Methods: For the study breast cancer patients were recruited from San Cecilio University Hospital in Granada (Spain) who were treated with trastuzumab. HER2 Ile655Val A˃G polimorphism was performed in 93 patients using Taqman SNP technology. We analyzed the relation of polymorphisms with disease free survival (DFS) and overall survival (OS). We also could asses 66 patients who had biochemical measurement of NTpro BNP during the treatment with trastuzumab and cardiovascular risk factors including diabetes, hypertension, smoking, hypercholesterolemia and body mass index (BMI). Cardiotoxicity was defined as a ≥ 10% decrease of the left ventricular ejection fraction (LVEF) from baseline, a LVEF below 40% or any clinical manifestation of heart insufficiency. NT-proBNP cut-off points were considered to stablish normal or abnormal values adjusted by patient age. Results: Genotype frequencies of HER2/neu 655 met Hardy-Weinberg equilibrium (p = 0.363). Logistic regression analysis adjusted by hormonal status and anthracycline treatment showed higher cardiotoxicity risk for AG vs AA Her2-Ile655 polimorphism (OR = 3.00, CI95% 1.07-8.41, p = 0.037) or for AG vs AA+GG Her2-Ile655 polimorphism (OR = 3.21, CI95% 1.15-8.96, p = 0.026). We did not find association between HER2neu Ile655Val polymorphism and DFS or OS. NT-proBNP baseline higher than the range (OR 5.9, 95% CI 1.2 - 28.5, p = 0.028) and diabetes mellitus (OR 22.0, 95% CI 5.7 - 85.4, p = 0.000) were found to be related with the development of cardiotoxicity. Conclusions: HER2-Ile655 A˃G polymorphism is significantly associated with higher risk of trastuzumab-induced cardiotoxicity but it is not correlated with DFS neither OS. Diabetes or baseline high NT-proBNP levels are predictors for the development of trastuzumab-induced cardiotoxicity. These parameters should be considered for a closer follow up and for preventive actions as accurate glycaemic control for patients who will receive trastuzumab.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1025-1025
Author(s):  
Isabel Blancas ◽  
Celia Martín ◽  
Marta Legerén ◽  
Michel Martos ◽  
Silvia Sequero ◽  
...  

1025 Background: HER2 overexpression in breast cancer is associated with a poor outcome, high risk of metastasis and a reduced overall survival. The introduction of Trastuzumab in the treatment scheme improved the prognosis of these patients. Nevertheless, around 20% of patients develop cardiotoxicity. The purpose of this study is to analyze the association of the HER2 Ile655Val A > G polymorphism with trastuzumab-induced cardiotoxicity and with survival. Methods: The study included 93 patients recruited from San Cecilio University Hospital in Granada (Spain) who were treated intravenously with Trastuzumab. The cardiotoxicity was diagnosed during the treatment follow-up considering a decrease of the left ventricular ejection fraction (LVEF) from baseline or clinical manifestation of congestive heart failure. HER2 655 A > G was genotyping using TaqMan SNP technology. Results: Genotype frequencies of HER2/neu 655 met Hardy-Weinberg equilibrium ( p= 0.363). We did not find differences in baseline LVEF in patients who developed cardiotoxicity vs those who did not. However, in cardiotoxicity group, the symptomatic patients had a baseline LVEF significantly lower than non-symptomatic patients (57.7 vs 66.1, p < 0.028). Logistic regression analysis adjusted by hormonal status and anthracycline treatment showed significant differences between AG and AA (OR = 3.00, CI95% 1.07-8.41, P= 0.037) or AG and AA+GG (OR = 3.21, CI95% 1.15-8.96, P= 0.026). However, we did not find association between Her2/neu Ile655Val polymorphism and disease-free survival or global survival. Conclusions: HER2 655 A > G polymorphism is significantly associated with higher risk of trastuzumab-induced cardiotoxicity but is not associated to a differential survival rate.


2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Fatemeh Zohrian ◽  
Azin Alizadehasl ◽  
Lida Zahedi ◽  
Homa Ghaderian ◽  
Robab Anbiaee ◽  
...  

Background: Human epidermal growth factor receptor 2(HER2) is a gene that makes proteins in the breast cell. The HER2 gene is present in about 25% - 30% of patients with breast cancers. The most common side effect of drugs is left ventricular dysfunction. Evaluation of left ventricular ejection fraction (LVEF) by 2D echocardiography cannot detect subtle changes in LV systolic function. Objectives: We want to draw a comparison between two groups of breast cancer patients (HER2 positive and negative) by advanced echocardiography. Methods: We have conducted a single center prospective study at Rajaie Cardiovascular Medical and Research Center in 2018 - 2019. Results: This analysis included 58 patients with breast cancer. 15 cases (34%) were HER2 positive. Mean left ventricular ejection fraction (2D LVEF) in HER2 positive patients was 55 % at baseline and in HER2 negative patients was 55 %. In HER2 positive patients we had 10 percent decrease in LVEF during follow-up and the final LVEF was about 45% (P value < 0.05). Mean left ventricular ejection fraction by 3D echocardiography (3D LVEF) in HER positive patients was 57 % and in HER2 negative patients was 55 % at baseline. In HER2 positive patients we had about 20% decrease in 3D LVEF and the final LVEF was 40 % (P value < 0.05). Mean circumferential strain (GCS) in HER2 positive patients was -21 and in HER2 negative patients was -21 at baseline which decreased to -18 in HER positive patients and -17 in HER2 negative patients, showing clinical significance ( P value = 0.008). Conclusions: In our study HER2 positive breast cancers showed about 10% drop in 2DEF, about 20% drop in 3DLVEF and about 5% drop in HMLVEF, which all were significant (P value < 0.05). We found that GCS is more sensitive than GLS in detecting subclinical involvement, and early changes in GCS is a good predictor of subsequent development of drugs (anthracycline-transtuzumab) induced cardiotoxicity.


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