Tumor Mutation Burden as a Potential Biomarker for PD-1/PD-L1 Inhibition in Advanced Non-small Cell Lung Cancer.


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.


Target Oncol


Targeted oncology


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 Y




Has Abstract


2020-02-01 00:00:00














  • Vitamin D Deficiency has a Negative Impact on Cetuximab-Mediated Cellular Cytotoxicity against Human Colon Carcinoma Cells.

    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


    authors: Mortara L,Gariboldi MB,Bosi A,Bregni M,Pinotti G,Guasti L,Squizzato A,Noonan DM,Monti E,Campiotti L

    更新日期:2018-10-01 00:00:00

  • Ongoing Response in BRAF V600E-Mutant Melanoma After Cessation of Intermittent Vemurafenib Therapy: A Case Report.

    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


    authors: Dooley AJ,Gupta A,Middleton MR

    更新日期:2016-08-01 00:00:00

  • Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment.

    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


    authors: Lassau N,Chebil M,Chami L,Bidault S,Girard E,Roche A

    更新日期:2010-03-01 00:00:00

  • Immunological Correlates of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma.

    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


    authors: Tzeng A,Diaz-Montero CM,Rayman PA,Kim JS,Pavicic PG Jr,Finke JH,Barata PC,Lamenza M,Devonshire S,Schach K,Emamekhoo H,Ernstoff MS,Hoimes CJ,Rini BI,Garcia JA,Gilligan TD,Ornstein MC,Grivas P

    更新日期:2018-10-01 00:00:00

  • Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study.

    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


    authors: Hong X,Song Y,Huang H,Bai B,Zhang H,Ke X,Shi Y,Zhu J,Lu G,Liebscher S,Cai C

    更新日期:2019-04-01 00:00:00

  • Expression and activity of EGFR in human cutaneous melanoma cell lines and influence of vemurafenib on the EGFR pathway.

    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


    authors: Gross A,Niemetz-Rahn A,Nonnenmacher A,Tucholski J,Keilholz U,Fusi A

    更新日期:2015-03-01 00:00:00

  • Clinical activity of sunitinib in patients with advanced desmoplastic round cell tumor: a case series.

    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


    authors: Italiano A,Kind M,Cioffi A,Maki RG,Bui B

    更新日期:2013-09-01 00:00:00

  • Designs and challenges for personalized medicine studies in oncology: focus on the SHIVA trial.

    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


    authors: Le Tourneau C,Kamal M,Trédan O,Delord JP,Campone M,Goncalves A,Isambert N,Conroy T,Gentien D,Vincent-Salomon A,Pouliquen AL,Servant N,Stern MH,Le Corroller AG,Armanet S,Rio Frio T,Paoletti X

    更新日期:2012-12-01 00:00:00

  • Tumours and tissues: similar homeostatic systems?

    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


    authors: Demicheli R

    更新日期:2013-06-01 00:00:00

  • Identification of driver mutations in lung cancer: first step in personalized cancer.

    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


    authors: Planchard D

    更新日期:2013-03-01 00:00:00

  • Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines.

    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


    authors: Hegde M,Mantelingu K,Pandey M,Pavankumar CS,Rangappa KS,Raghavan SC

    更新日期:2016-10-01 00:00:00

  • Hyperbaric oxygen therapy and cancer--a review.

    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


    authors: Moen I,Stuhr LE

    更新日期:2012-12-01 00:00:00

  • Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia.

    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


    authors: Scott LJ

    更新日期:2019-10-01 00:00:00

  • Targeting insulin-like growth factor type 1 receptor in cancer therapy.

    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


    authors: Atzori F,Traina TA,Ionta MT,Massidda B

    更新日期:2009-12-01 00:00:00

  • Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between theory and practice.

    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


    authors: Saponara M,Pantaleo MA,Nannini M,Biasco G

    更新日期:2012-12-01 00:00:00

  • Management of Adverse Events During Rucaparib Treatment for Relapsed Ovarian Cancer: A Review of Published Studies and Practical Guidance.

    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


    authors: Lorusso D,García-Donas J,Sehouli J,Joly F

    更新日期:2020-06-01 00:00:00

  • Serum Alpha1-Globulin as a Novel Prognostic Factor in Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors.

    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


    authors: Chen X,Yao J,Liu L,Zheng W,Hu X,Zhu Y,Wang H,Guo J

    更新日期:2019-04-01 00:00:00

  • Delta-catenin promotes the proliferation and invasion of colorectal cancer cells by binding to E-cadherin in a competitive manner with p120 catenin.

    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


    authors: Zhang H,Dai SD,Zhang D,Liu D,Zhang FY,Zheng TY,Cui MM,Dai CL

    更新日期:2014-03-01 00:00:00

  • The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review.

    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


    authors: Nichetti F,Marra A,Corti F,Guidi A,Raimondi A,Prinzi N,de Braud F,Pusceddu S

    更新日期:2018-06-01 00:00:00

  • Activity and safety of erlotinib as second- and third-line treatment in elderly patients with advanced non-small cell lung cancer: a phase II trial.

    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


    authors: Rossi D,Dennetta D,Ugolini M,Catalano V,Alessandroni P,Giordani P,Baldelli AM,Casadei V,Graziano F,Luzi Fedeli S

    更新日期:2010-12-01 00:00:00

  • Detection of KIT and PDGFRA mutations in the plasma of patients with gastrointestinal stromal tumor.

    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


    authors: Kang G,Bae BN,Sohn BS,Pyo JS,Kang GH,Kim KM

    更新日期:2015-12-01 00:00:00

  • Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy.

    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


    authors: Fucà G,Galli G,Poggi M,Lo Russo G,Proto C,Imbimbo M,Vitali M,Ganzinelli M,Lanti C,Molino G,Stangoni F,Zilembo N,de Braud F,Garassino MC,Signorelli D

    更新日期:2018-12-01 00:00:00

  • Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.

    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


    authors: Kato H,de Souza P,Kim SW,Lickliter JD,Naito Y,Park K,Kumar S,Mugundu GM,Bang YJ

    更新日期:2020-02-01 00:00:00

  • Vemurafenib-induced progression of breast cancer: a case report and review of the literature.

    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


    authors: Novik AV,Protsenko SA,Baldueva IA,Ivantsov AO,Nekhaeva TL,Akhaeva ZY,Yanus GA,Iyevleva AG,Imyanitov EN

    更新日期:2016-04-01 00:00:00

  • EGFR intron-1 CA repeat polymorphism is a predictor of relapse and survival in complete resected only surgically treated esophageal cancer.

    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


    authors: Vashist YK,Trump F,Gebauer F,Kutup A,Güngör C,Kalinin V,Muddasar R,Vettorazzi E,Yekebas EF,Brandt B,Pantel K,Izbicki JR

    更新日期:2014-03-01 00:00:00

  • Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24).

    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


    authors: Farolfi A,Petrone M,Scarpi E,Gallà V,Greco F,Casanova C,Longo L,Cormio G,Orditura M,Bologna A,Zavallone L,Ventriglia J,Franzese E,Loizzi V,Giardina D,Pigozzi E,Cioffi R,Pignata S,Giorda G,De Giorgi U

    更新日期:2018-08-01 00:00:00

  • Is There a Survival Benefit of First-Line Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitor Monotherapy Versus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer?: A Meta-Analysis.

    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


    authors: Guetz GD,Landre T,Uzzan B,Chouahnia K,Nicolas P,Morere JF

    更新日期:2016-02-01 00:00:00

  • Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma.

    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


    authors: Dhillon S

    更新日期:2017-04-01 00:00:00

  • Renal Toxicities of Targeted Therapies.

    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


    authors: Abbas A,Mirza MM,Ganti AK,Tendulkar K

    更新日期:2015-12-01 00:00:00

  • Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    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


    authors: Heigener DF,Pereira JR,Felip E,Mazal J,Manzyuk L,Tan EH,Merimsky O,Sarholz B,Esser R,Gatzemeier U

    更新日期:2015-06-01 00:00:00