Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer

Mooter, Tom Van den; Teuwen, Laure-Anne; Rutten, Annemie; Dirix, Luc

doi:10.1517/14712598.2015.1036026

Cited by 5 publications

(9 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ADCs, consisting of monoclonal antibodies conjugated to potent chemotherapeutics via a stable linker, have given rise to a highly efficacious class of anticancer drugs [ 2 ]. Currently, there are two ADCs approved, one for the treatment of relapsed/refractory Hodgkin’s lymphoma and systemic anaplastic large cell lymphoma (brentuximab vedotin) [ 3 ], and the other for advanced/metastatic human epidermal growth factor receptor 2–positive breast cancer (trastuzumab emtansine) [ 4 ]. In addition, there is a rapidly growing clinical pipeline with over 60 ADCs in development to target a wide range of blood cancers and solid tumors [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study

et al. 2018

View full text Add to dashboard Cite

PurposeThis phase 1 dose-escalation portion of the study evaluated the safety, pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC).Materials and MethodsAdult patients with advanced GI malignancies expressing GCC (H-score ≥ 10) received TAK-264 on day 1 of 3-week cycles as 30-minute intravenous infusions for up to 1 year or until disease progression or unacceptable toxicity. The primary objectives were to evaluate the safety profile including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum tolerated dose (MTD), and characterize the PK profile of TAK-264.ResultsTwelve patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8 mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1 to 10). None of the patients experienced a DLT and the MTD was not determined. Ten patients (83%) experienced adverse events (AEs). The most common were neutropenia, anorexia, and nausea (each reported by four patients). Five patients (42%) experienced grade ≥ 3 AEs consisting of tumor hemorrhage and hypertension, ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK-264 increased proportionally with the dose and the median half-life was approximately 5.5-6.6 days. No patients experienced an objective response.ConclusionTAK-264 demonstrated a manageable safety profile with limited antitumor activity consistent with studies conducted in Western patients with advanced GI malignancies. TAK-264 exposure increased proportionally with the dose.

show abstract

Section: Introductionmentioning

confidence: 99%

TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study

et al. 2018

View full text Add to dashboard Cite

show abstract

“…This likely contributes to the overall safety profile of T-DM1. 33 , 38 , 39 Finally, Yu et al 27 have concluded that the regimen of T-DM1 as well as pertuzumab in combination with trastuzumab and docetaxel is efficacious with fewer side effects as compared with other regimens through a network meta-analysis of six HER2-targeted treatment drugs and one naive standard treatment. Although that article only included a clinical study of T-DM1, it has been shown that T-DM1 is a better regimen.…”

Section: Discussionmentioning

confidence: 99%

Clinical efficacy and safety of T-DM1 for patients with HER2-positive breast cancer

Blankenstein¹,

Ma²,

Wang³

et al. 2016

OTT

View full text Add to dashboard Cite

PurposeThe aim of this study was to evaluate the therapeutic efficacy and safety of trastuzumab emtansine (T-DM1) for the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer.MethodsWe performed a systemic review and meta-analysis of the relevant published clinical studies. A computerized search was performed for controlled clinical trials of T-DM1 in targeted treatment. Overall survival, progression-free survival, objective response rate, symptom progression free, and adverse events (AEs) were evaluated.ResultsEight eligible trials with a total of 2,016 patients with breast cancer were included in the present meta-analysis. The treatment of patients with breast cancer with T-DM1 was associated with significantly increased overall and progression-free survival when compared with controls (P<0.0001). An analysis of the objective response rate and symptom progression free also demonstrated favorable results for T-DM1 treatment (P≤0.0001). There was no significant difference between the T-DM1 and control groups with respect to nonhematologic or hematologic AEs (P=0.99 and P=0.30, respectively).ConclusionOverall, T-DM1 is efficacious in the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer and low rates of AEs compared with controls.

show abstract

“…These three compounds are well‐known tubulin inhibitors and both vincristine and vinblastine are routinely used to treat cancer patients whose cancer belongs to various histopathological types. Ado‐trastuzumab emtansine (T‐DM1) is a human epidermal growth factor receptor 2 (HER2) targeted antibody–drug conjugate composed of trastuzumab, a stable linker (4‐( N ‐maleimidomethyl)cyclohexane‐1‐carboxylate, MCC), and the cytotoxic agent DM1, which is mertansine, a derivative of maytansine . T‐DM1 underwent several successful Phase III clinical trials and it is now proposed as a treatment of choice in second line and beyond for patients with advanced HER2‐expressing breast cancer …”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

View full text Add to dashboard Cite

The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

show abstract

Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer

Abstract: T-DM1 (Kadcyla) has become the treatment of choice in second-line and beyond for patients with advanced HER2-expressing breast cancer.

Cited by 5 publications

References 51 publications

TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study

TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study

Clinical efficacy and safety of T-DM1 for patients with HER2-positive breast cancer

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Contact Info

Product

Resources

About