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 reported to benefit from PD-1/PD-L1 inhibitors. However, additional biomarkers are needed, and whether tumor mutation burden (TMB) can be a robust biomarker or not is still controversial. OBJECTIVE:We conducted this study to assess TMB as a biomarker for PD-1/PD-L1 inhibitor treatment in advanced NSCLC patients in a real-world setting. PATIENTS AND METHODS:Chinese NSCLC patients who received a PD-1/PD-L1 inhibitor at the People's Liberation Army General Hospital and who had pathological tissues available for TMB were retrospectively analyzed. Demographic and clinical information were evaluated. Targeted next-generation sequencing (NGS) of the tumor tissue was performed. The relationship between TMB and clinical benefit was assessed. RESULTS:Thirty-four patients treated with PD-1/PD-L1 inhibitors between March 2015 and January 2019 were analyzed. The TMB was greater in patients with complete response (CR)/partial response (PR) versus stable disease (SD) versus progressive disease (PD) (median 11 vs. 9.7 vs. 4.2 mutations/megabase [Mb]; p = 0.049). The median progression-free survival was 10.6 months in the TMB-high group versus 3.9 months in the TMB-low group (cut-off value = 10 mutations/Mb) (hazard ratio [HR] 0.26 [95% confidence interval 0.12-0.57], p = 0.0007). The median overall survival was 21.0 months and 11.6 months (HR 0.37 [0.17-0.81], p = 0.0126) in the TMB-high group and the TMB-low group, respectively. The disease control rate was higher in the TMB-high group than in the TMB-low group (100% vs. 70%, p = 0.024). CONCLUSIONS:High TMB was associated with a better outcome in advanced NSCLC patients who received PD-1/PD-L1 inhibitors in China. Further studies are needed to confirm our findings.
journal_name
Target Oncoljournal_title
Targeted oncologyauthors
Huang D,Zhang F,Tao H,Zhang S,Ma J,Wang J,Liu Z,Cui P,Chen S,Huang Z,Wu Z,Zhao L,Hu Ydoi
10.1007/s11523-020-00703-3subject
Has Abstractpub_date
2020-02-01 00:00:00pages
93-100issue
1eissn
1776-2596issn
1776-260Xpii
10.1007/s11523-020-00703-3journal_volume
15pub_type
杂志文章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::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::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::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::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::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: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: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:Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor. It is synergistic with chemotherapy in preclinical models. We hypothesized that sunitinib in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) would be a tolerable and effective regimen in advanced gastric and gastroesophageal jun...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-019-00692-y
更新日期:2020-02-01 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: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: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::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::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::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::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::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: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 wer...
journal_title:Targeted oncology
pub_type: 杂志文章,meta分析,收录出版
doi:10.1007/s11523-015-0376-7
更新日期:2016-02-01 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:BACKGROUND:Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. OBJECTIVE:We conducted this study to explore the prognostic value of SPF in patient...
journal_title:Targeted oncology
pub_type: 杂志文章
doi:10.1007/s11523-019-00625-9
更新日期:2019-04-01 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::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::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 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: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: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: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 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::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::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