Metronomic Chemotherapy for Metastatic Breast Cancer

2021 ◽  
pp. 1-6
Author(s):  
Slavomir Krajnak ◽  
Marco J. Battista ◽  
Annette Hasenburg ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Best Supportive Care ◽  
Chemotherapeutic Agents ◽  
Her2 Positive ◽  
Continuous Administration ◽  
Leading Role

Background: As disease control and quality of life play a leading role in metastatic breast cancer (MBC), metronomic chemotherapy (MCT) is gaining popularity alongside conventional chemotherapy (CCT) and targeted therapies. Summary: MCT, defined as continuous administration of low-dose chemotherapeutic agents, is accepted as a therapy that exerts its effects via immunomodulation, anti-angiogenesis and direct cytotoxic effects. Oral administration of MCT is safe, easy to handle, and allows for flexible drug dosing. Dose accumulations associated with non-tolerable side effects are rare, so the medication can be administered for longer periods of time. Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic disease resistant to endocrine-based therapy and not requiring rapid tumor response are generally suitable for MCT. However, MCT may also be promising in patients with triple-negative and HER2-positive tumors without aggressive disease who prefer a lower toxicity profile compared to CCT. The most commonly used agents are cyclophosphamide (CTX), methotrexate (MTX), capecitabine (CAPE), and vinorelbine (VRL), whereby a combination of agents is frequently applied. Key Messages: Based on the growing body of evidence, MCT can be considered as a suitable treatment option in selected MBC patients. Nevertheless, there is an urgent need for randomized controlled trials comparing MCT with CCT, but also with best supportive care. Due to the multimodal mechanisms of action, the combination with targeted and immunological therapies may represent a new promising approach for the treatment of MBC.

Indium-111–Labeled Trastuzumab Scintigraphy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

2006 ◽  
Vol 24 (15) ◽  
pp. 2276-2282 ◽  
Author(s):  
Patrick J. Perik ◽  
Marjolijn N. Lub-De Hooge ◽  
Jourik A. Gietema ◽  
Winette T.A. van der Graaf ◽  
M. Alexander de Korte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Myocardial Uptake ◽  
Her2 Positive ◽  
Indium 111 ◽  
Epidermal Growth

Purpose The cardiac and antineoplastic effects of trastuzumab may be related to specific uptake of trastuzumab in myocardium and tumor tissue, respectively. We evaluated whether indium-111 (111In) –labeled trastuzumab scintigraphy can predict cardiotoxicity and identify tumor lesions. In addition, we evaluated whether plasma markers for cardiac dysfunction can be used to predict cardiotoxicity. Patients and Methods Patients with human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer underwent gamma camera imaging from 15 minutes to 7 days after injection of 150 MBq 111In–diethylenetriamine penta-acetic acid anhydride (DTPA) –trastuzumab, after loading-dose trastuzumab, and after once-a-week trastuzumab doses for 11 weeks, and concomitant paclitaxel once every 3 weeks. Cardiac assessments were performed before treatment, and after four and six cycles. Plasma N-terminal probrain natriuretic peptide (NT-proBNP) and serum troponin I were measured with immunoassay. Results Fifteen of the 17 patients were available for cardiac and tumor uptake analysis. On the first scan, myocardial 111In-DTPA-trastuzumab uptake was observed in one patient with pre-existing cardiac arrhythmias, who did not develop heart failure during treatment. Severe cardiotoxicity occurred in three patients, without initial myocardial uptake, whereas one showed weak myocardial uptake after four cycles. The detection rate of single tumor lesions was 45%. New tumor lesions were discovered in 13 of 15 patients. Pretreatment plasma NT-proBNP levels were higher in patients with than without heart failure (mean, 534 [standard deviation, 236] v 105 [standard deviation, 79] ng/L; P = .009). Conclusion Radiolabeled trastuzumab scintigraphy was not valuable in predicting trastuzumab-related cardiotoxicity in metastatic breast cancer patients, but can identify HER2-positive tumors. Measurement of plasma NT-proBNP is promising regarding prediction of trastuzumab-related cardiotoxicity.

A Phase II Study of Trastuzumab Emtansine in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Who Were Previously Treated With Trastuzumab, Lapatinib, an Anthracycline, a Taxane, and Capecitabine

2012 ◽  
Vol 30 (26) ◽  
pp. 3234-3241 ◽  
Author(s):  
Ian E. Krop ◽  
Patricia LoRusso ◽  
Kathy D. Miller ◽  
Shanu Modi ◽  
Denise Yardley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Epidermal Growth

Purpose To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) –targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies. Patients and Methods In this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety. Results Among 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4 months), and median duration of response was 7.2 months (95% CI, 4.6 months to not estimable). In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to 52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse events were grades 1 to 2; the most frequent grade ≥ 3 events were thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%). Conclusion T-DM1 is well tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapy agents. T-DM1 may be an effective new treatment for this patient population.

Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: An Integrated Safety Analysis

2014 ◽  
Vol 32 (25) ◽  
pp. 2750-2757 ◽  
Author(s):  
Véronique Diéras ◽  
Nadia Harbeck ◽  
G. Thomas Budd ◽  
Joel K. Greenson ◽  
Alice E. Guardino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Grade 3

Purpose The antibody–drug conjugate trastuzumab emtansine (T-DM1) combines the cytotoxic activity of DM1 with the human epidermal growth factor receptor 2 (HER2) –targeted, antitumor properties of trastuzumab. T-DM1 has shown activity in phase I and II single-arm studies in patients with pretreated HER2-positive metastatic breast cancer (MBC) and has demonstrated superior efficacy and improved tolerability versus standard MBC treatments in randomized phase II and III studies. This analysis, combining available data from all single-agent T-DM1 studies to date, was conducted to better define the T-DM1 safety profile. Patients and Methods Six studies in patients with HER2-positive MBC who received T-DM1 3.6 mg/kg every 3 weeks and follow-up data from patients in an extension study were analyzed. Analyses included adverse events (AEs) by grade; AEs leading to death, drug discontinuation, or dose reduction; and select AEs. Results Among 884 T-DM1–exposed patients, the most commonly reported all-grade AEs were fatigue (46.4%), nausea (43.0%), thrombocytopenia (32.2%), headache (29.4%), and constipation (26.5%). The most common grade 3 to 4 AEs were the laboratory abnormalities of thrombocytopenia (11.9%) and increased AST serum concentration (4.3%). These were manageable and not generally associated with clinical symptoms. There were 12 AE-related deaths. AEs resulted in dose reductions in 17.2% of patients and drug discontinuations in 7.0%. Conclusion In this analysis of 884 T-DM1–exposed patients, grade 3 or greater AEs were infrequent and typically asymptomatic and manageable. This favorable safety profile makes T-DM1 treatment suitable for exploration in other breast cancer settings.

scholarly journals Duration of trastuzumab in patients with HER2-positive metastatic breast cancer in prolonged remission

2016 ◽  
Vol 23 (2) ◽  
pp. 91 ◽  
Author(s):  
R. Haq ◽  
P. Gulasingam
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Online Survey ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Good Prognosis ◽  
Her2 Positive ◽  
Treatment Practices ◽  
Trastuzumab Therapy

Background Outcomes in metastatic breast cancer (mbc) positive for her2 (human epidermal growth factor receptor 2) are generally unfavourable. Trastuzumab has revolutionized the prognosis of her2-positive mbc. Some her2-positive mbc patients go into prolonged remission, and a few patients remain in remission even after discontinuation of trastuzumab, suggesting the possibility of a cure. In our practice, 4 her2-positive mbc patients treated with chemotherapy and trastuzumab have remained in remission on maintenance therapy for 5 years or more. Of those 4 patients, 2 have continued in remission after discontinuation of trastuzumab for more than 1 year. The objective of the present paper was therefore to address the duration of trastuzumab therapy in her2-positive mbc patients in prolonged remission.Methods We conducted a literature review of the duration of trastuzumab in her2-positive mbc patients in remission. We also conducted an online survey of oncologists in Ontario to determine their treatment practices in her2-positive mbc patients.Results The literature search found no specific evidence about the optimal duration of trastuzumab maintenance therapy in her2-positive mbc in prolonged remission. However, retrospective studies suggest predictive markers of good prognosis in patients in complete remission taking maintenance trastuzumab. Identifying those markers could lead to more personalized treatment. Our survey of oncologists about their treatment practices in her2-positive mbc patients revealed that 82.93% of respondents (n = 34) follow the currently available guidelines.Conclusions With the emergence of patients in prolonged remission, duration of trastuzumab in her2-positive mbc has become an important and relevant clinical question worldwide. Collaborative efforts are needed for the further study of this topic.

Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study

2012 ◽  
Vol 30 (21) ◽  
pp. 2585-2592 ◽  
Author(s):  
Kimberly L. Blackwell ◽  
Harold J. Burstein ◽  
Anna Maria Storniolo ◽  
Hope S. Rugo ◽  
George Sledge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Heavily Pretreated ◽  
Epidermal Growth

Purpose Phase III EGF104900 data demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival (PFS) and clinical benefit rate versus lapatinib monotherapy, offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer (MBC). Final planned overall survival (OS) analysis from EGF104900 is reported here. Patients and Methods Patients with HER2-positive MBC whose disease progressed during prior trastuzumab-based therapies were randomly assigned to receive lapatinib monotherapy or lapatinib in combination with trastuzumab. OS and updated PFS data are presented using Kaplan-Meier curves and log-rank tests stratified for hormone receptor and visceral disease status. Subgroup analyses were conducted to identify characteristics of patients deriving the greatest clinical benefit. Results In this updated final analysis of all patients randomly assigned with strata (n = 291), lapatinib plus trastuzumab continued to show superiority to lapatinib monotherapy in PFS (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .011) and offered significant OS benefit (HR, 0.74; 95% CI, 0.57 to 0.97; P = .026). Improvements in absolute OS rates were 10% at 6 months and 15% at 12 months in the combination arm compared with the monotherapy arm. Multiple baseline factors, including Eastern Cooperative Oncology Group performance status of 0, nonvisceral disease, < three metastatic sites, and less time from initial diagnosis until random assignment, were associated with improved OS. Incidence of adverse events was consistent with previously reported rates. Conclusion These data demonstrated a significant 4.5-month median OS advantage with the lapatinib and trastuzumab combination and support dual HER2 blockade in patients with heavily pretreated HER2-positive MBC.

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