Tumor mutation burden predicts response and survival to immune checkpoint inhibitors: a meta-analysis

被引:9
作者
Wan, Linghong [1 ,2 ,3 ]
Wang, Zhi [1 ,2 ,3 ]
Xue, Jinmin [1 ,2 ,3 ]
Yang, Huaju [1 ,2 ,3 ]
Zhu, Yuxi [1 ,2 ,3 ]
机构
[1] Chongqing Med Univ, Dept Oncol, Affiliated Hosp 1, Chongqing, Peoples R China
[2] Chongqing Med Univ, Dept Oncol, Affiliated Hosp 1, Jinshan Hosp, Chongqing, Peoples R China
[3] Chongqing Clin Canc Res Ctr, Chongqing, Peoples R China
关键词
Tumor mutation burden (TMB); immune checkpoint inhibitors (ICIs); predictive biomarker; meta-analysis; LIGAND; 1; PD-L1; GASTRIC-CANCER; CELL; EXPRESSION; BIOMARKER; BLOCKADE; EFFICACY; OUTCOMES; TMB;
D O I
10.21037/tcr-20-1131
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Cancer is one of the world's top three causes of death now. Immune checkpoint inhibitors (ICIs) show encouraging ability to treat some malignancies due to its long-term efficacy and low side effects. However, the predictive biomarker of the immunotherapy efficacy has been inconclusive. Thus, exploring new biomarkers is important. Methods: A meta-analysis was conducted to evaluate whether tumor mutation burden (TMB) could be a predictive biomarker of the efficacy of ICIs. Using the PubMed and Cochrane Library databases, we searched for articles about TMB and the prognosis of patients with multiple malignancies conducted from 1984 to May 22, 2020. We identified the relationship between TMB and the clinical efficacy of ICIs by using Stata 12.1 software. Results: Eighteen articles with a total of 4,535 patients were included in this meta-analysis. Results showed that high-TMB patients had better progression-free survival (PFS) than low-TMB patients with cancer treated with ICIs (HR =0.45; 95% CI: 0.36-0.56, P= 0.002). Moreover, high-TMB patients had longer overall survival (OS) than low-TMB patients. However, the heterogeneity was extremely high, so the result regarding OS was meaningless (HR =0.56; 95% CI: 0.44-0.70, P=0.000, I-squares: 72.6%). Conclusions: Our study indicates that high TMB is associated with better PFS. Thus, TMB can be considered as a predictive marker of PFS of patients treated with ICIs in the future.
引用
收藏
页码:5437 / 5449
页数:13
相关论文
共 41 条
  • [1] Tumor mutational burden assessed by targeted NGS predicts clinical benefit from immune checkpoint inhibitors in non-small cell lung cancer[J]. Alborelli, Ilaria;Leonards, Katharina;Rothschild, Sacha, I;Leuenberger, Laura P.;Prince, Spasenija Savic;Mertz, Kirsten D.;Poechtrager, Severin;Buess, Martin;Zippelius, Alfred;Laubli, Heinz;Haegele, Jasmin;Tolnay, Markus;Bubendorf, Lukas;Quagliata, Luca;Jermann, Philip. JOURNAL OF PATHOLOGY, 2020(01)
  • [2] Immune Checkpoint Protein Inhibition for Cancer: Preclinical Justification for CTLA-4 and PD-1 Blockade and New Combinations[J]. Baksh, Kathryn;Weber, Jeffrey. SEMINARS IN ONCOLOGY, 2015(03)
  • [3] Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer[J]. Barroso-Sousa, Romualdo;Keenan, Tanya E.;Pernas, Sonia;Exman, Pedro;Jain, Esha;Garrido-Castro, Ana C.;Hughes, Melissa;Bychkovsky, Brittany;Umeton, Renato;Files, Janet L.;Lindeman, Neal I.;MacConaill, Laura E.;Hodi, F. Stephen;Krop, Ian E.;Dillon, Deborah;Winer, Eric P.;Wagle, Nikhil;Lin, Nancy U.;Mittendorf, Elizabeth A.;Van Allen, Eliezer M.;Tolaney, Sara M. CLINICAL CANCER RESEARCH, 2020(11)
  • [4] PD-L1 is an independent prognostic predictor in gastric cancer of Western patients[J]. Boeger, Christine;Behrens, Hans-Michael;Mathiak, Micaela;Krueger, Sandra;Kalthoff, Holger;Roecken, Christoph. ONCOTARGET, 2016(17)
  • [5] First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer[J]. Carbone, D. P.;Reck, M.;Paz-Ares, L.;Creelan, B.;Horn, L.;Steins, M.;Felip, E.;van den Heuvel, M. M.;Ciuleanu, T. -E.;Badin, F.;Ready, N.;Hiltermann, T. J. N.;Nair, S.;Juergens, R.;Peters, S.;Minenza, E.;Wrangle, J. M.;Rodriguez-Abreu, D.;Borghaei, H.;Blumenschein, G. R.;Villaruz, L. C.;Havel, L.;Krejci, J.;Corral Jaime, J.;Chang, H.;Geese, W. J.;Bhagavatheeswaran, P.;Chen, A. C.;Socinski, M. A. NEW ENGLAND JOURNAL OF MEDICINE, 2017(25)
  • [6] Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden[J]. Chalmers, Zachary R.;Connelly, Caitlin F.;Fabrizio, David;Gay, Laurie;Ali, Siraj M.;Ennis, Riley;Schrock, Alexa;Campbell, Brittany;Shlien, Adam;Chmielecki, Juliann;Huang, Franklin;He, Yuting;Sun, James;Tabori, Uri;Kennedy, Mark;Lieber, Daniel S.;Roels, Steven;White, Jared;Otto, Geoffrey A.;Ross, Jeffrey S.;Garraway, Levi;Miller, Vincent A.;Stephens, Phillip J.;Frampton, Garrett M. GENOME MEDICINE, 2017
  • [7] Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy[J]. Cristescu, Razvan;Mogg, Robin;Ayers, Mark;Albright, Andrew;Murphy, Erin;Yearley, Jennifer;Sher, Xinwei;Liu, Xiao Qiao;Lu, Hongchao;Nebozhyn, Michael;Zhang, Chunsheng;Lunceford, Jared;Joe, Andrew;Cheng, Jonathan;Webber, Andrea L.;Ibrahim, Nageatte;Plimack, Elizabeth R.;Ott, Patrick A.;Seiwert, Tanguy;Ribas, Antoni;McClanahan, Terrill K.;Tomassini, Joanne E.;Loboda, Andrey;Kaufman, David. SCIENCE, 2018(6411)
  • [8] BRAF Mutant NSCLC: Correlation with PD-L1 Expression, TMB, MSI and Response to ICPi and Anti-BRAF Therapy[J]. Dudnik, E.;Peled, N.;Wollner, M.;Onn, A.;Agbareya, A.;Nechushtan, H.;Kuznetsov, T.;Roisman, L.;Rozenblum, A. Belilovski;Geva, S.;Zer, A.;Bar, J. JOURNAL OF THORACIC ONCOLOGY, 2017(11)
  • [9] Rare targetable drivers (RTDs) in non-small cell lung cancer (NSCLC): Outcomes with immune check-point inhibitors (ICPi)[J]. Dudnik, Elizabeth;Bshara, Elias;Grubstein, Ahuva;Fridel, Ludmila;Shochat, Tzippy;Roisman, Laila C.;Ilouze, Maya;Rozenblum, Anna Belilovski;Geva, Smadar;Zer, Alona;Rotem, Ofer;Allen, Aaron M.;Peled, Nir. LUNG CANCER, 2018
  • [10] Comprehensive Genomic Profiling Identifies Novel Genetic Predictors of Response to Anti-PD-(L)1 Therapies in Non-Small Cell Lung Cancer[J]. Fang, Wenfeng;Ma, Yuxiang;Yin, Jiani C.;Hong, Shaodong;Zhou, Huaqiang;Wang, Ao;Wang, Fufeng;Bao, Hua;Wu, Xue;Yang, Yunpeng;Huang, Yan;Zhao, Hongyun;Shao, Yang W.;Zhang, Li. CLINICAL CANCER RESEARCH, 2019(16)