Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

New developments in the treatment of metastatic gastric cancer: focus on trastuzumab.

ABSTRACT: Patients with metastatic gastric cancer have a poor outcome. The development of new combinations of chemotherapy has led to steady but only modest gains in overall survival with largest effects reported with two- and three-drug regimens. Trastuzumab, a fully humanized monoclonal antibody directed at the human epidermal growth factor receptor-2 (HER2), has been found to improve response rate and survival in patients with advanced gastric cancer. This update will review the role of HER2 and summarize therapeutic advances in the use of trastuzumab in advanced gastric cancer.

SUBMITTER: Rose JS

PROVIDER: S-EPMC3084304 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

New developments in the treatment of metastatic gastric cancer: focus on trastuzumab.

Rose Jeffrey S JS Bekaii-Saab Tanios S TS

OncoTargets and therapy 20110324

Patients with metastatic gastric cancer have a poor outcome. The development of new combinations of chemotherapy has led to steady but only modest gains in overall survival with largest effects reported with two- and three-drug regimens. Trastuzumab, a fully humanized monoclonal antibody directed at the human epidermal growth factor receptor-2 (HER2), has been found to improve response rate and survival in patients with advanced gastric cancer. This update will review the role of HER2 and summar ...[more]

PMID: 21552412

Similar Datasets

New drug developments in metastatic gastric cancer.

Project description:Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

| S-EPMC6236851 | biostudies-literature

Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan.

Project description:Nanoliposomal irinotecan (nal-IRI) was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy) trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin) in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in survival.

| S-EPMC4821390 | biostudies-literature

Metastatic gastric cancer - focus on targeted therapies.

Project description:Gastric cancer (GC) is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.

| S-EPMC3395896 | biostudies-other

New developments in the treatment of advanced squamous cell lung cancer: focus on afatinib.

Project description:Until recently, few treatment options existed for the treatment of squamous cell carcinoma (SqCC) of the lung, especially in the second-line setting following platinum-based chemotherapy. Accordingly, outcomes in this subtype of non-small-cell lung cancer (NSCLC) were generally poor. In this context, the recent availability of the checkpoint inhibitors nivolumab and pembrolizumab, the anti-VEGFR2 antibody ramucirumab (combined with docetaxel), and the ErbB-family blocker afatinib for the treatment of relapsed/refractory SqCC of the lung represent major advances. However, the rapid expansion of the treatment armamentarium invites many questions regarding optimal treatment choice and sequence in individual patients. This review focuses on the biologic rationale and clinical evidence to support the use of afatinib in this treatment setting, highlighting the prominent role of the ErbB-signaling cascade in SqCC tumors. The seminal Phase III LUX-Lung 8 study, on which the approval of afatinib is based, is discussed and contextualized with the emergence of immunotherapies. Finally, criteria are explored that might drive physicians' treatment decisions when considering the use of afatinib based on individual patient characteristics. Other ongoing developments in the treatment of SqCC of the lung that will lead to further options and welcome improvements in the management of this difficult-to-treat disease are summarized.

| S-EPMC5436789 | biostudies-literature

New developments in targeted therapy for metastatic colorectal cancer.

Project description:Colorectal cancer (CRC) is the second most lethal cancer worldwide and the prognosis of metastatic CRC (mCRC) remains poor. Recent advancements in translational research have led to the identification of several new therapeutic targets and improved the treatment outcome of patients with tumours harbouring BRAF V600E mutation, (HER2) ErBB2 alterations, NTRK gene fusions and KRAS(G12C) mutation. Improved understanding towards the mechanism of resistance to targeted therapy such as anti-epidermal growth factor receptor antibodies and the evolving role of therapeutic monitoring with circulating tumour DNA (ctDNA) has enabled the longitudinal tracking of clonal evolution during treatment and the individualization of subsequent treatments. To broaden the community-based implementation of precision oncology in directing targeted therapies for patients with gastrointestinal cancers including mCRC, the feasibility of 'Master Protocols' that utilizes ctDNA-based genotyping platforms is currently being evaluated. Such protocols encompass both observational and interventional clinical trials of novel targeted therapies conducted within a large clinical trial network. In this review, we will discuss the latest developments in targeted therapies, and therapeutic strategies for overcoming acquired drug resistance in patients with mCRC.

| S-EPMC9846305 | biostudies-literature

Recent developments in the treatment of metastatic colorectal cancer.

Project description:Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS/tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease. Even with few new targeted agents receiving approval in CRC, the incorporation of next-generation sequencing into clinical decision making represents an important step forward. Biomarkers such as BRAF mutations, microsatellite instability, and HER2 amplification represent promising molecular aberrations with therapies in various stages of development, and highlight the importance of companion diagnostics in supporting targeted agents. In this review, we will discuss the importance of incorporating biomarkers into clinical decision making and regimen selection in CRC. We will particularly focus on the recent evidence suggesting an important role for tumor location in selecting first-line therapy, the importance of recent advances in biomarker development and molecular subtyping, as well as recently approved agents (regorafenib and TAS-102) and promising targeted agents that have the potential to change the standard of care.

| S-EPMC5524248 | biostudies-literature

New advancements and developments in treatment of renal cell carcinoma: focus on pazopanib.

Project description:With the recent approval of pazopanib, an oral multitargeted tyrosine kinase inhibitor which potently targets vascular endothelial growth factor receptors 1-3, platelet-derived growth factor, and c-kit, six agents are now available for use in the management of metastatic renal cell carcinoma (RCC). Pazopanib has shown improved progression-free survival compared with placebo in treatment-naïve or cytokine-treated patients with metastatic RCC in large Phase II and Phase III clinical trials. Pazopanib has demonstrated a tolerable side effect profile and is currently being compared with sunitinib in a Phase III noninferiority trial. In this review, the outcomes of the clinical testing of pazopanib are discussed, as well as a perspective on the placement of pazopanib among other approved agents.

| S-EPMC2962303 | biostudies-literature

Treatment of metastatic colorectal cancer: focus on panitumumab.

Project description:Targeted agents are an important therapeutic option in the treatment of metastatic colorectal cancer (mCRC). Panitumumab is a recombinant, fully humanized, immunoglobulin G2 monoclonal antibody that targets the epidermal growth factor receptor (EGFR) with efficacy in mCRC as monotherapy and in combination with chemotherapy. Kirsten rat sarcoma (KRAS) mutation status has emerged as an important biomarker to predict response to anti-EGFR therapy. Optimal timing for panitumumab use in the mCRC treatment algorithm has not been established. This review discusses the mechanism of action, predictive biomarkers, and role of panitumumab in the treatment of mCRC.

| S-EPMC4484697 | biostudies-literature

Identification of targets and new developments in the treatment of multiple sclerosis--focus on cladribine.

Project description:Orally available disease-modifying drugs for relapsing-remitting multiple sclerosis (MS) represent an unmet need for this chronic and debilitating disease. Among 5 currently investigated drugs at phase 3 clinical stage, promising efficacy data for fingolimod and oral cladribine have recently been published. However, benefits need to be weighed against the risks to define the role of these compounds within current treatment regimens. In this review, data on the efficacy of a promising compound, oral cladribine, are discussed and balanced with known and anticipated risks in a postmarketing era, and finally gives an outlook on the potential place of this drug in treatment algorithms for MS in the future.

| S-EPMC2915536 | biostudies-literature

Real-World Treatment Patterns and Economic Burden Following First-Line Trastuzumab in Patients with Metastatic Gastric Cancer in the USA.

Project description:BackgroundTrastuzumab in combination with chemotherapy is the standard first-line (1L) treatment for HER2+ metastatic gastric cancer (mGC) in the USA.ObjectiveThis study characterizes the real-world treatment patterns, healthcare resource use (HRU), and costs in patients with HER2+ mGC post-1L trastuzumab before approval of fam-trastuzumab deruxtecan-nxki.Patients and methodsThis retrospective study used the IQVIA PharMetrics® Plus Database (October 2014-September 2019) to identify adults with HER2+ mGC who discontinued trastuzumab-based regimens in 1L. Patient characteristics, second-line (2L) treatment patterns, and treatment duration were summarized. HRU and costs before and after discontinuation of 1L trastuzumab-based regimens as well as during 2L treatment were described.ResultsOf the 190 HER2+mGC patients who discontinued 1L trastuzumab-based regimens, 136 (71.58%) initiated 2L treatments. Trastuzumab-based regimens were the most common in 2L (50.74%), followed by ramucirumab + paclitaxel (19.85%). The median time to 2L discontinuation was 2.37 months. During a mean follow-up of 9.8 months, mean per-patient-per-month (PPPM) healthcare costs post-1L trastuzumab-based regimens were higher in patients receiving 2L treatment than those without subsequent treatment (US$25,178 vs. US$14,812). The mean PPPM cost during 2L treatment was US$30,838, primarily driven by outpatient infusion costs (US$22,262).ConclusionsThe short duration of 2L treatment observed in this study is consistent with a lack of effective treatments post-1L trastuzumab prior to 2020. Re-use of trastuzumab treatment was common despite its limited efficacy and high treatment cost. The findings highlight the unmet medical needs and substantial burden faced by patients with HER2 +mGC previously treated with trastuzumab.

| S-EPMC10491560 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data