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 rationale suggests a prognostic role for inflammatory biomarkers for ICI-treated patients with mGOJ/GC. OBJECTIVE:Our objective was to assess whether inflammatory markers are associated with survival in ICI-treated patients with mGOJ/GC. METHODS:Ten inflammatory markers were retrospectively analyzed at baseline in 57 patients with mGOJ/GC with unknown PD-L1 status treated with second-line ICIs and correlated with OS. Selected variables were then analyzed in a multivariate Cox-regression model and used to build a GIPI nomogram. RESULTS:Neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) as continuous variables and albumin categorized as less than versus greater than 30 g/dL were the most significant predictors of OS and were used to build the GIPI nomogram. Nomogram-based lowest, mid-low, mid-high, and highest risk quartiles were associated with median OS (mOS) of 14.9, 7.1, 5.6, and 2.1 months, respectively (hazard ratio [HR] of highest vs. lowest risk 4.94; p = 0.0002). By optimally dichotomizing CRP and NLR, patients with one or more of the risk factors NLR > 6, CRP > 15 mg/L, and albumin < 30 g/dL (n = 29) had an mOS of 3.9 versus 14.2 months for patients with no risk factor (n = 28) (HR 2.48; p = 0.0015). CONCLUSIONS:GIPI, combining NLR, CRP, and albumin, is the first inflammatory index with a significant prognostic value in patients with mOGJ/GC receiving ICIs. GIPI merits validation in independent cohorts and prospective clinical trials.
journal_name
Target Oncoljournal_title
Targeted oncologyauthors
Formica V,Morelli C,Patrikidou A,Murias C,Butt S,Nardecchia A,Lucchetti J,Renzi N,Shiu KK,Roselli M,Arkenau HTdoi
10.1007/s11523-020-00723-zsubject
Has Abstractpub_date
2020-06-01 00:00:00pages
327-336issue
3eissn
1776-2596issn
1776-260Xpii
10.1007/s11523-020-00723-zjournal_volume
15pub_type
杂志文章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::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::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: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 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:BACKGROUND:Golgi phosphoprotein 2 (GOLPH2) has been shown to be involved in chronic inflammatory processes and carcinogenesis. GOLPH2 is prominently overexpressed in hepatocellular carcinoma, melanoma, glioblastoma, prostate, lung, and colorectal cancer. With a low and tightly regulated expression in non-malignant tiss...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-019-00667-z
更新日期:2019-10-01 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
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::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::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::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::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::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::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: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::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::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::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::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: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: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::Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with poor outcome occurring in adolescents and young adults. Therapeutic options for patients with advanced disease are limited. Preclinical studies have shown that VEGFR-2 and VEGFA are overexpressed in DSRCT and that DSRCT xenografts wer...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-012-0251-8
更新日期:2013-09-01 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::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::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: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::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::Sorafenib (Nexavar®) is currently the only systemic agent approved for use in hepatocellular carcinoma (HCC). Its approval was based on the results of the pivotal SHARP and Sorafenib Asia-Pacific (AP) trials in Child-Pugh (CP) class A patients with advanced HCC, which showed significantly longer median overall surviva...
journal_title:Targeted oncology
pub_type: 杂志文章,评审
doi:10.1007/s11523-017-0484-7
更新日期:2017-04-01 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: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