scholarly journals Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive Breast Cancer Patients

Breast Care ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. 401-408 ◽  
Author(s):  
Lidia Kowalczyk ◽  
Rupert Bartsch ◽  
Christian F. Singer ◽  
Alex Farr
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Targeted Therapies ◽  
Kinase Inhibitor ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Anti Tumor Activity ◽  
Positive Breast Cancer

The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1). T-DM1 combines the anti-tumor activity of trastuzumab with that of DM1, a highly potent derivative of the anti-microtubule agent maytansine, resulting in increased anti-tumor activity. Notably, this agent has been demonstrated to be safe and is associated with low toxicity rates. However, maytansinoid, the cytotoxic component of T-DM1, does have the potential to induce various adverse events, particularly radiation necrosis, when used in combination with stereotactic radiosurgery. In this review, we aimed to summarize the current literature regarding T-DM1 safety and toxicity, with special emphasis on the existing landmark studies.

scholarly journals Targeted Therapies in HER2-Positive Breast Cancer - a Systematic Review

Breast Care ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Amelie Schramm ◽  
Nikolaus De Gregorio ◽  
Peter Widschwendter ◽  
Visnja Fink ◽  
Jens Huober
Keyword(s):  
Breast Cancer ◽  
Targeted Therapies ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Increased Risk ◽  
Positive Breast Cancer

About 20% of all breast cancer patients have a human epidermal growth factor receptor 2 (HER2)-positive breast tumor. This entity underwent an impressive change in prognosis, with notable improvement of progression-free survival and overall survival. Due to more aggressive tumors and no specific therapy, HER2 overexpression was historically seen as a negative prognostic marker, with worse prognosis and increased risk of recurrent disease. Trastuzumab, the first anti-HER2 antibody, revolutionized the systemic therapy options in HER2-positive breast cancer and initiated several targeted therapies and more personalized treatment strategies. Over the years, multiple HER2-targeting drugs stepped into clinical practice, for the curative as well as the metastatic situation. This review summarizes the targeted treatment options in HER2-positive breast cancer and their current impact in the clinical routine. Results of the most outstanding trials in HER2-targeted therapies and important ongoing trials are subsequently described for an up-to-date overview.

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.

Neratinib for the treatment of early-stage, hormone receptor-positive, HER2-overexpressed breast cancer

2020 ◽  
Vol 16 (17) ◽  
pp. 1165-1177
Author(s):  
Yolanda Jerez ◽  
Blanca Herrero ◽  
Marta Arregui ◽  
Blanca Morón ◽  
Miguel Martín ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Future Directions ◽  
Her2 Positive Breast Cancer ◽  
Hormone Receptor Positive ◽  
Positive Breast Cancer

HER2-positive breast cancer accounts for 18–20% of all breast cancers. Despite significant advances and the currently available adjuvant treatments for management of the disease, approximately 25% of HER2-positive early-stage breast cancer patients show relapse and die. Neratinib is an irreversible tyrosine kinase inhibitor. Multiple studies have reported its significant antitumor activity in metastatic HER2-positive breast cancer. It is administered orally and has also been tested in the adjuvant setting. In this article, we present a comprehensive review of the pharmacokinetics and pharmacodynamics of neratinib as well as its clinical efficacy, with an emphasis on early HER2-positive breast cancer and suggestions for future directions for neratinib research.

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 Trastuzumab Emtansine for Her2 Positive Breast Cancer Patients: an Updated Systematic Review

2015 ◽  
Vol 18 (7) ◽  
pp. A816 ◽  
Author(s):  
PM Valle ◽  
GB Mosegui ◽  
CM Vianna ◽  
RL Araújo ◽  
T Felicissimo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Cancer Patients ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Risk of hepatotoxicity with trastuzumab emtansine in breast cancer patients: a systematic review and meta-analysis

2020 ◽  
Vol 11 ◽  
pp. 204209862091505 ◽  
Author(s):  
Amani M. Cobert ◽  
Catherine Helms ◽  
Chris Larck ◽  
Donald C. Moore
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Meta Analysis ◽  
High Grade ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Increased Risk ◽  
Positive Breast Cancer

Background: Trastuzumab emtansine (T-DM1) is an anti-HER2 antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. One of the most severe adverse events reported with T-DM1 is hepatotoxicity. The objective of our meta-analysis is to investigate the risk of hepatic adverse events in patients with breast cancer receiving T-DM1 compared with controls. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing T-DM1 with a control treatment in patients with HER2-positive breast cancer. Phase II/III RCTs with available event number or event rate of hepatic toxicity with an assessable sample size were included. Relative risk (RR) and corresponding 95% confidence intervals (CI) for all grade and high-grade (grade 3/4) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations were calculated. Results: Seven RCTs were deemed eligible and were included in the meta-analysis. The RR for all-grade AST and ALT elevations were 3.24 (95% CI 2.16–4.86; p < 0.00001) and 2.90 (95% CI 1.98–4.23; p < 0.00001), respectively. The RR for high-grade AST and ALT elevations were 2.73 (95% CI 1.07–6.93; p = 0.03) and 2.17 (95% CI 1.34–3.50; p = 0.002), respectively. Conclusions: Our meta-analysis demonstrates that T-DM1-based therapy is associated with an increased risk of AST and ALT elevations.

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