The Clinical Efficacy and Cardiotoxicity of Fixed-Dose Monthly Trastuzumab in HER2-Positive Breast Cancer: A Single Institutional Analysis

Abstract

ObjectiveTrastuzumab-containing treatment regimens have been shown to improve survival outcomes in HER2-positive breast cancer (BC). It is much easier to infuse a fixed one-vial dose to every patient on a regular schedule in the general clinical setting. The aims of this study were evaluating the efficacy of a 440 mg fixed-dose of trastuzumab administered on a monthly infusion schedule, and the risk factors for cardiac events.Patients and methodsWe retrospectively reviewed data from 300 HER2-positive BC patients in our institute: 208 were early-stage BC patients undergoing adjuvant trastuzumab treatment, and 92 were metastatic BC patients treated with trastuzumab infusions until disease progression. There were 181 patients receiving regular trastuzumab infusions every 3 weeks (Q3W; 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks), and the other 119 patients were treated monthly with a fixed 440 mg dose (QM; fixed 440 mg every 4 weeks).ResultsThe medians of progression-free survival (PFS) and overall survival (OS) in the adjuvant setting were not reached in both treatment groups. In the metastatic setting, there was no significant difference between groups in PFS or OS. The median time to significant cardiovascular (CV) dysfunction was 4.54 months. The incidence of congestive heart failure requiring medication in our cohort was 3.4%.ConclusionIn our study, we found that fixed-dose monthly trastuzumab was feasible and effective. In addition, the CV risk was not higher with the fixed-dose protocol. This treatment modality could lower the cost and was easier to implement in clinical practice. Larger prospective randomized studies with longer-term follow up are needed to confirm our results.

Management of Breast Cancer During the COVID-19 Pandemic: A Stage- and Subtype-Specific Approach

“…65,66 To decrease frequent visits for those receiving H 6 P, we offer extending the dosing interval from 3 weeks to 4 weeks, especially if receiving other treatments every 4 weeks. 67 We advise caution in the use of therapies with high risk of pulmonary toxicity, such as immunotherapy for metastatic TNBC 68 or trastuzumab deruxtecan for HER2-positive MBC. 69 For HR-positive MBC, we generally continue ET and targeted therapies that are well tolerated.…”

African Vegetables (Clerodendrum volubile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab-Induced Cardiotoxicity in Wistar Rats

“…Trastuzumab has been reported to dysregulate HER2 signaling pathways and suppress autophagy by activating autophagy-inhibitory Erk/mTOR/Ulk 1 signaling cascade in cardiomyocytes and overtly resulting in the massive mitochondrial and toxic reactive oxygen species (ROS) accumulation in human cardiomyocytes [ 6 , 7 ]. As a clinical strategy of preventing the development of trastuzumab-induced cardiotoxicity, Wu et al [ 8 ] recently investigated and reported the clinical efficacy and attenuation of trastuzumab-induced cardiac dysfunction in HER2-positive breast cancer patients using fixed 440 mg dose monthly administration of trastuzumab. Unfortunately, till date, there are no approved effective therapeutic agent(s) available that could prevent the development of this unwanted/adverse effect of trastuzumab without comprising its efficacy.…”

Is the Fixed-Dose Intravenous Trastuzumab Policy Warranted in Limited-Resource Settings?

“…Currently, there are no prospective studies evaluating the clinical efficacy of fixed-dose intravenous regimens. One retrospective study from Taiwan 4 compared the efficacy and safety of weight-based and fixed-dose regimens. Data from 181 patients who received regular weight-based TRA every 3 weeks were compared with that from 119 patients who received monthly fixed doses of 440 mg every 4 weeks as part of adjuvant or palliative treatment.…”