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 histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression. PATIENTS AND METHODS:EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations. RESULTS:Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0-1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746-750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7-19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2-36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4-35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05). CONCLUSIONS:Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.
journal_name
Target Oncoljournal_title
Targeted oncologyauthors
Cardona AF,Arrieta O,Zapata MI,Rojas L,Wills B,Reguart N,Karachaliou N,Carranza H,Vargas C,Otero J,Archila P,Martín C,Corrales L,Cuello M,Ortiz C,Pino LE,Rosell R,Zatarain-Barrón ZL,CLICaP.doi
10.1007/s11523-017-0497-2subject
Has Abstractpub_date
2017-08-01 00:00:00pages
513-523issue
4eissn
1776-2596issn
1776-260Xpii
10.1007/s11523-017-0497-2journal_volume
12pub_type
杂志文章abstract:BACKGROUND:A consistent percentage of patients with metastatic non-small cell lung cancer (NSCLC) derives no or only marginal benefit from immunotherapy (IO). OBJECTIVE:Since serum sodium has been linked to both prognosis in NSCLC and modulation of immune cells activity, we aimed to assess the association between low ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-018-0599-5
更新日期:2018-12-01 00:00:00
abstract::In subsets of gastrointestinal stromal tumors (GISTs), mutations of the KIT and PDGFRA receptor tyrosine kinases correlate with tumor prognosis and response to tyrosine kinase inhibitors (TKIs). Determining genotypes in TKI-resistant GISTs is challenging due to the potential risks and limitations of repeated biopsies ...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-015-0361-1
更新日期:2015-12-01 00:00:00
abstract::Vemurafenib, a specific inhibitor of mutated BRAF kinase, may activate wild-type BRAF and therefore induce squamous cell skin carcinomas in patients treated for melanoma. All vemurafenib clinical trials excluded patients with multiple primary malignant tumors; therefore, the action of this drug on concurrent BRAF wild...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-015-0384-7
更新日期:2016-04-01 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::Obinutuzumab (Gazyva®, Gazyvaro®) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-017-0485-6
更新日期:2017-04-01 00:00:00
abstract::With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal tox...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-015-0368-7
更新日期:2015-12-01 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::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:BACKGROUND:In 2017, nivolumab monotherapy was shown to be effective as third- or later-line therapy in patients with advanced gastric or gastroesophageal junction cancer. OBJECTIVE:In this study, we investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the outcomes of nivolumab monotherapy...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-020-00716-y
更新日期:2020-06-01 00:00:00
abstract::The selective BRAF inhibitors vemurafenib and dabrafenib yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Treatment traditionally continues until disease progression or the development of unacceptable toxicity. Acquired drug resistance and toxicity are key...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-015-0410-9
更新日期:2016-08-01 00:00:00
abstract::The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) inv...
journal_title:Targeted oncology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s11523-014-0336-7
更新日期:2015-06-01 00:00:00
abstract::Elderly and poor performance status advanced non-small cell lung cancer (NSCLC) patients often tolerate chemotherapy poorly. Special approaches are needed for these patient populations. Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), erlotinib and gefitinib, are active agents in the t...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-009-0104-2
更新日期:2009-01-01 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::ABP 980 was developed as a biosimilar to trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2), that is indicated for the treatment of HER2-positive metastatic breast cancer, early breast cancer (EBC), and metastatic gastric cancer. ABP 980 is approved in the United States, Europ...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-019-00675-z
更新日期:2019-12-01 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::Venetoclax (Venclyxto®; Venclexta®) is a first-in-class, oral, selective B cell lymphoma-2 (BCL-2) inhibitor. The drug is approved in numerous countries, including those of the EU and in the USA, for the treatment of adults with relapsed or refractory (RR) chronic lymphocytic leukemia (CLL); the specific indication(s)...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-019-00673-1
更新日期:2019-10-01 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::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::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::δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily whose normal pattern of expression is restricted to the brain. Similar to p120ctn, δ-catenin can bind to the juxtamembrane domain of E-cadherin. We examined the expression of δ-catenin, p120ctn, and E-cadherin using immunohistochemistry in 95 cases o...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-013-0269-6
更新日期:2014-03-01 00:00:00
abstract::Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) catalyze the first rate-limiting step in the oxidative metabolism of compounds containing indole rings, including the transformation of the essential amino acid L-tryptophan to N-formyl-L-kynurenine. Through direct and indirect means, IDO exerts bo...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-017-0547-9
更新日期:2018-04-01 00:00:00
abstract::Atezolizumab (Tecentriq®), a humanized, anti-programmed cell death ligand-1 (PD-L1) monoclonal antibody, in combination with bevacizumab, carboplatin and paclitaxel (ABCP) or with carboplatin and nab-paclitaxel (ACnP) has been approved as first-line treatment for metastatic nonsquamous NSCLC, based on results from the...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-019-00686-w
更新日期:2019-12-01 00:00:00
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::Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Efficacy of this drug was documented in the BR.21 trial showing that adenocarcinoma, female gender, Asian ethnicity and never-smoker status are predictive of clinical response to erlotinib. Retrospective studies documented the same bene...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-010-0163-4
更新日期:2010-12-01 00:00:00
abstract::Data regarding the expression of epidermal growth factor receptor (EGFR) in melanoma and its role in the tumor biology are conflicting. In BRAF V600-mutant melanomas, the expression of EGFR has been associated with acquired resistance to BRAF inhibitors. In this study, we assessed EGFR expression and downstream signal...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-014-0318-9
更新日期:2015-03-01 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:Axitinib, an inhibitor of vascular endothelial growth factor (VEGF) receptors, is approved as second-line treatment for advanced renal cell carcinoma (RCC). Agents targeting the VEGF pathway may induce renal toxicities, which may be influenced by pre-existing renal dysfunction. OBJECTIVE:The objective was t...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-015-0389-2
更新日期:2016-04-01 00:00:00
abstract::Several angiogenesis inhibitors have been approved for commercial use and many additional agents are under development for the treatment of various malignancies. Cardiovascular toxicities have been increasingly recognized as effects of this entire class of new anticancer therapeutics. There is a limited but growing un...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-009-0106-0
更新日期:2009-04-01 00:00:00
abstract::It is believed that the insulin-like growth factor receptor type 1 (IGF-1R) signaling pathway plays a pivotal role in cancer growth, progression, and resistance to anticancer therapies. Strategies are being developed to block IGF-1R as an anticancer treatment. We reviewed several potential strategies for disrupting th...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-009-0123-z
更新日期:2009-12-01 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