Abstract:
OBJECTIVE:To determine the efficacy of first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in molecularly selected patients with advanced non-small cell lung cancer (NSCLC), we performed this pooled analysis. METHOD:Randomized trials of EGFR-TKIs as treatment for advanced NSCLC were included for this meta-analysis. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs in the selected patients by EGFR-mutation status were calculated. RESULTS:Out of 2134 retrieved articles, 30 randomized controlled trials (RCTs) enrolling more than 4053 patients with wild-type EGFR tumors and 1592 patients with mutant EGFR tumors were identified. For EGFR mutant patients, EGFR-TKIs treatment improved progression-free survival (PFS) compared with chemotherapy: the summary HRs were 0.41 (p < 0.00001) for the first-line setting and 0.46 (p = 0.02) for second/third-line setting, respectively. Also, the same superior trend was found with TKIs maintenance over placebo (HR = 0.14, p < 0.00001) and with TKIs combined with chemotherapy over chemotherapy (HR = 0.49, p = .002) in both the first-line and maintenance therapy settings. For EGFR wild-type patients, EGFR-TKIs have fared worse than chemotherapy in the first-line setting (HR = 1.65, p = .03) and in the second/third-line setting (HR = 1.27, p = .005). However, EGFR-TKIs maintenance still produced a reduction of 19 % in the risk of progression over placebo (HR = 0.81, p = .02). Furthermore, EGFR-TKIs added to chemotherapy as first-line treatment resulted in an improvement of PFS over chemotherapy alone in such wild-type EGFR patients (HR = 0.82, p = .03). In overall survival (OS) analysis, only EGFR-TKIs single agent was inferior to chemotherapy in EGFR wild-type patients (HR = 1.13, p = .02). No statistically significant difference in terms of OS was observed in any other subgroup analysis. CONCLUSIONS:For EGFR mutant patients, EGFR-TKIs therapy produced a prominent PFS benefit in all settings. Among EGFR wild-type patients, EGFR-TKIs were inferior to chemotherapy both for first-line treatment and for second/third-line treatment. However, EGFR-TKIs maintenance and addition of EGFR-TKIs to chemotherapy could provide additive benefit over chemotherapy alone in such EGFR wild-type patients.
journal_name
Target Oncoljournal_title
Targeted oncologyauthors
Liu J,Sheng Z,Zhang Y,Li Gdoi
10.1007/s11523-015-0376-7subject
Has Abstractpub_date
2016-02-01 00:00:00pages
49-58issue
1eissn
1776-2596issn
1776-260Xpii
10.1007/s11523-015-0376-7journal_volume
11pub_type
杂志文章,meta分析,收录出版abstract:BACKGROUND:Tyrosine-kinase inhibitors (TKIs) markedly improve progression-free survival (PFS) of patients with advanced non-small-cell lung cancer (NSCLC) mutated for epidermal growth factor receptor (EGFR). Results on overall survival (OS) are less clear-cut. We performed a publication-based meta-analysis to address f...
journal_title:Targeted oncology
pub_type: 杂志文章,meta分析
doi:10.1007/s11523-015-0373-x
更新日期:2016-02-01 00:00:00
abstract::Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma a...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-012-0233-x
更新日期:2012-12-01 00:00:00
abstract::Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that may occur in patients receiving anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab and tyrosine kinase inhibitors. Little is known about the characteristics of patients at risk for PRES under anti-VEGF agen...
journal_title:Targeted oncology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s11523-011-0201-x
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking. OBJECTIVE:The MITO group conducted a...
journal_title:Targeted oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11523-018-0574-1
更新日期:2018-08-01 00:00:00
abstract::Among neuroendocrine carcinomas of the gut, well-differentiated tumors are highly vascularized, featuring specific characteristics on contrast-enhanced imaging. Well-differentiated neuroendocrine tumors spontaneously harbor hypervascular enhancement, coexisting with areas of necrosis mainly located at the center of tu...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-012-0216-y
更新日期:2012-06-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer diagnosed worldwide. HCC occurs due to chronic liver disease and is often diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are currently used as first-line agents for HCC therapy, but these are non-selective cytotox...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-016-0452-7
更新日期:2017-02-01 00:00:00
abstract::Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an i...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-015-0412-7
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL. OBJECTIVE:As the distribution of PTCL subtypes differs between populations and few p...
journal_title:Targeted oncology
pub_type: 杂志文章,多中心研究
doi:10.1007/s11523-019-00630-y
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations. OBJECTIVE:The purpose of this study was to assess...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-017-0497-2
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients. OBJECTIVE:This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients wi...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00701-5
更新日期:2020-02-01 00:00:00
abstract::The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it should be retained th...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-012-0221-1
更新日期:2012-12-01 00:00:00
abstract::Chemotherapy represents the mainstay of non-small cell lung cancer (NSCLC) treatment, but response is usually observed in only one out of three patients. Massive efforts have been carried out to identify biomarkers that might help clinicians to choose appropriate drugs, by identifying potentially sensitive subjects an...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-010-0132-y
更新日期:2010-03-01 00:00:00
abstract::Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker a...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-018-0567-0
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Immunotherapy based on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors has revolutionized the treatment of non-small cell lung cancer (NSCLC). Patients with high PD-L1 expression or DNA mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) cancer are re...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00703-3
更新日期:2020-02-01 00:00:00
abstract::The poly(ADP-ribose) polymerase inhibitor rucaparib is approved as monotherapy in the treatment and maintenance settings for women with relapsed ovarian cancer in the European Union and the United States. We review the safety profile of rucaparib in both settings and provide recommendations for the clinical management...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00715-z
更新日期:2020-06-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) has recently been associated with interesting molecular characteristics that have important implications in carcinogenesis and response to targeted therapies. Targeted therapies, if given to a patient subpopulation enriched by the presence of relevant molecular targets, can often abr...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-013-0263-z
更新日期:2013-03-01 00:00:00
abstract::In anticancer drug development, there has been increasing consideration for the potential of a compound to cause adverse electrocardiographic changes, especially QT interval prolongation, which can be associated with risk of torsades de pointes and sudden death. Irrespective of overt clinical toxicities, QTc assessmen...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-014-0325-x
更新日期:2015-03-01 00:00:00
abstract::Personalized medicine is defined by the National Cancer Institute as "a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease." In oncology, the term "personalized medicine" arose with the emergence of molecularly targeted agents. The prescript...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-012-0237-6
更新日期:2012-12-01 00:00:00
abstract::The currently prevalent somatic mutation theory of carcinogenesis and metastases explicitly assumes that cancer is a cellular disease, i.e. a disease of the control of cell proliferation and/or cell differentiation. Accordingly, explanations should always be sought for at a gene and/or gene product level, regardless o...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-013-0277-6
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00723-z
更新日期:2020-06-01 00:00:00
abstract::The ubiquitin (Ub)+proteasome proteolytic pathway is responsible for the selective degradation of the majority of nuclear and cytosolic proteins. The proteasome is a high molecular weight multicatalytic protease that serves as the catalytic core of the complex Ub-dependent protein degradation pathway and is an excitin...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-010-0165-2
更新日期:2010-12-01 00:00:00
abstract::The discovery of chemoresistant cancer stem cells (CSCs) in carcinomas has created the need for therapies that specifically target these subpopulations of cells. Here, we characterized a bispecific targeted toxin that is composed of two antibody fragments and a catalytic protein toxin allowing it to bind two CSC marke...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-013-0290-9
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:Cancer is a multifactorial disease, which makes it difficult to cure. Since more than one defective cellular component is often involved during oncogenesis, combination therapy is gaining prominence in the field of cancer therapeutics. OBJECTIVE:The purpose of this study was to investigate the combinatorial...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-016-0441-x
更新日期:2016-10-01 00:00:00
abstract::The influence of tumor infiltrating lymphocytes on tumor growth and response to therapy is becoming increasingly apparent. While much work has focused on the role of T cell responses in anti-tumor immunity, the role of B cells in solid tumors is much less understood. Tumor infiltrating B cells have been found in a var...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-017-0481-x
更新日期:2017-04-01 00:00:00
abstract::Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-009-0124-y
更新日期:2009-12-01 00:00:00
abstract::We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected fr...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-014-0356-3
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE:We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-018-0595-9
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND:Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epide...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-018-0586-x
更新日期:2018-10-01 00:00:00
abstract::Basal transcription regulation of the epidermal growth factor receptor is dependent upon a CA simple sequence repeat polymorphism in the intron-1 (CA-SSR-1). Here, we evaluate the role of CA-SSR-1 in complete resected esophageal cancer (EC) patients without neoadjuvant or adjuvant treatment. Genomic DNA was extracted ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-013-0260-2
更新日期:2014-03-01 00:00:00
abstract::Dynamic contrast-enhanced ultrasonography (DCE-US) is a new functional technique enabling a quantitative assessment of solid tumor perfusion using raw linear data. DCE-US allows the calculation of parameters as slope of wash-in or area under the curve (AUC) representing, respectively, blood flow or blood volume. Reduc...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-010-0136-7
更新日期:2010-03-01 00:00:00