Association of tumour mutational burden with outcomes in patients with select advanced solid tumours treated with pembrolizumab in KEYNOTE-158
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KEYNOTE-158 discovered that pembrolizumab is effective in various types of cancers with TMB ≥10 mut/Mb, particularly solid cancers.
“KEYNOTE-158 discovered that Pembrolizumab, as an ICI, is effective in various types of cancers with TMB ≥10 mut/Mb, particularly solid cancers [111].”
From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [111]
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Immune Checkpoint Inhibitors in Cancer Therapy
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“KEYNOTE-158 discovered that Pembrolizumab, as an ICI, is effective in various types of cancers with TMB ≥10 mut/Mb, particularly solid cancers [111].”
BackgroundThe Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker
Jardim, D. L., Goodman, A., de Melo Gagliato, D., & Kurzrock, R. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.10.001 · Cited by 1,192 · see citing works
Beyond immune checkpoint blockade: emerging immunological strategies
Kubli, S. P., Berger, T., Araújo, D. V., Siu, L. L., & Mak, T. W. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00155-y · Cited by 460 · see citing works
Clinical cancer genomic profiling
Chakravarty, D., & Solit, D. B. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00338-8 · Cited by 227 · see citing works
Precision medicine in non-small cell lung cancer: Current applications and future directions
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Zhou, K. I., Peterson, B. F., Serritella, A. V., Thomas, J., Reizine, N. M., Moya, S. M., Tan, C., Wang, Y., & Catenacci, D. V. T. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2085 · Cited by 196 · see citing works
“A post hoc analysis was performed using a binary cutoff at 10 mut/Mb given the recent FDA approval (13).”
BackgroundMethodBiomarkers in Triple-Negative Breast Cancer: State-of-the-Art and Future Perspectives
Cocco, S., Piezzo, M., Calabrese, A., Cianniello, D., Caputo, R., Lauro, V. D., Fusco, G., Gioia, G. D., Licenziato, M., & Laurentiis, M. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21134579 · Cited by 121 · see citing works
Shonka, D. C., Ho, A., Chintakuntlawar, A. V., Geiger, J. L., Park, J. C., Seetharamu, N., Jasim, S., Abdelhamid Ahmed, A. H., Bible, K. C., Brose, M. S., et al. (2022) · Head & Neck · doi:10.1002/hed.27025 · Cited by 117 · see citing works
“The importance of molecular alterations and signaling pathways in thyroid cancer has led to the development of new targeted therapeutic drugs within the last decade, affording much needed treatment options for patients with advanced DTC. Statement 11: Multikinase inhibitors such as lenvatinib should be offered for the…”
ResultInfluentialPredictive biomarkers for response to immune checkpoint inhibition
Shum, B., Larkin, J., & Turajlic, S. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.036 · Cited by 117 · see citing works
Huang, R. S. P., Haberberger, J., Severson, E. A., Duncan, D. L., Hemmerich, A. C., Edgerly, C. I., Ferguson, N. L., Williams, E. A., Elvin, J. A., Vergilio, J., et al. (2020) · Modern Pathology · doi:10.1038/s41379-020-00664-y · Cited by 113 · see citing works
“Tumor mutational burden (TMB) is promising as a predictive biomarker for PD-L1/PD-1 immunotherapies, and recently, studies with pembrolizumab monotherapy have shown clinical benefit in a pan-tumor setting with a TMB cutoff of 10 mutations/Mb [11, 12].”
BackgroundImmunotherapy in Colorectal Cancer: Current and Future Strategies
Ooki, A., Shinozaki, E., & Yamaguchi, K. (2021) · Journal of the Anus Rectum and Colon · doi:10.23922/jarc.2020-064 · Cited by 109 · see citing works
Brown, L. C., Tucker, M. D., Sedhom, R., Schwartz, E. B., Zhu, J., Kao, C., Labriola, M., Gupta, R. T., Marin, D., Wu, Y. S., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001792 · Cited by 105 · see citing works
Gogas, H., Dréno, B., Larkin, J., Demidov, L., Stroyakovskiy, D., Eroglu, Z., Francesco Ferrucci, P., Pigozzo, J., Rutkowski, P., Mackiewicz, J., et al. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2020.12.004 · Cited by 102 · see citing works
Salivary Gland Carcinoma: Novel Targets to Overcome Treatment Resistance in Advanced Disease
Villeneuve, L. D., Souza, I. L., Tolentino, F. D. S., Ferrarotto, R., & Schvartsman, G. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.580141 · Cited by 94 · see citing works
Pooled ctDNA analysis of MONALEESA phase III advanced breast cancer trials
André, F., Su, F., Solovieff, N., Hortobágyi, G. N., Chia, S., Neven, P., Bardia, A., Tripathy, D., Lu, Y.-S., Lteif, A., et al. (2023) · Annals of Oncology · doi:10.1016/j.annonc.2023.08.011 · Cited by 98 · see citing works
The Role of Immune Checkpoint Inhibitors in Cancer Therapy
Basudan, A. (2022) · Clinics and Practice · doi:10.3390/clinpract13010003 · Cited by 94 · see citing works
“In addition, the KEYNOTE-158 study, which mainly covered about 10 malignancies (mostly solid tumors), has revealed significant response of patients with TMB-H to pembrolizumab [101].”
BackgroundFidelle, M., Yonekura, S., Picard, M., Cogdill, A. P., Hollebecque, A., Roberti, M. P., & Zitvogel, L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.600886 · Cited by 82 · see citing works
“Thus, pembrolizumab is FDA approved for TMB-high tumors (96).”
BackgroundCurrent Status and Future Perspective of Immunotherapy in Gastrointestinal Cancers
Lü, Z., Peng, Z., Liu, C. X., Wang, Z., Wang, Y., Jiao, X., Li, J., & Shen, L. (2020) · The Innovation · doi:10.1016/j.xinn.2020.100041 · Cited by 81 · see citing works
Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges
Qian, J. M., & Schoenfeld, J. D. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.608772 · Cited by 81 · see citing works
“Tumor mutational burden, a potential surrogate for tumor neoantigens that can be recognized by the immune system, is one such biomarker, leading to the first ever histology-agnostic FDA approval of the PD-1 inhibitor pembrolizumab for mismatch repair deficient tumors of any histology (14, 15), though there is increasi…”
BackgroundRischin, D., Gil-Martín, M., González-Martı́n, A., Braña, I., Hou, J. Y., Cho, D., Falchook, G. S., Formenti, S. C., Jabbour, S. K., Moore, K. N., et al. (2020) · Gynecologic Oncology · doi:10.1016/j.ygyno.2020.08.026 · Cited by 75 · see citing works
Pedersen, K. S., Foster, N. R., Overman, M. J., Boland, P. M., Kim, S. S., Arrambide, K. A., Jaszewski, B. L., Bekaii‐Saab, T., Graham, R. P., Welch, J., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0159 · Cited by 66 · see citing works
“This finding was independently reached prior to the recent tumor-agnostic FDA approval of pembrolizumab for where TMB ≥10 mt/MB, which was approved on the basis of data fromnon-SBA tumor histologies onKEYNOTE-158 (26).”
BackgroundSelf-citationCurrent status of immunotherapy for advanced gastric cancer
Kawazoe, A., Shitara, K., Boku, N., Yoshikawa, T., & Terashima, M. (2020) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyaa202 · Cited by 61 · see citing works
Choosing tumor mutational burden wisely for immunotherapy: A hard road to explore
Li, R., Han, D., Shi, J., Han, Y., Tan, P., Zhang, R., & Li, J. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188420 · Cited by 56 · see citing works
Hoefflin, R., Lazarou, A., Hess, M. E., Reiser, M., Wehrle, J., Metzger, P., Frey, A. V., Becker, H., Aumann, K., Berner, K., et al. (2021) · Cancers · doi:10.3390/cancers13051151 · Cited by 59 · see citing works
“Of note, the positive results of the Keynote-158 study [71,73] led to a tumor-agnostic FDA-approval for pembrolizumab in June 2020 [5] reflecting one essential aspect of the MTB, namely, to provide patients early access to promising drugs not yet approved.”
ResultPembrolizumab for advanced penile cancer: a case series from a phase II basket trial
Hahn, A. W., Chahoud, J., Campbell, M. T., et al. (2021) · Investigational New Drugs · doi:10.1007/s10637-021-01100-x · Cited by 56 · see citing works
Identification and Utilization of Biomarkers to Predict Response to Immune Checkpoint Inhibitors
Gjoerup, O. V., Brown, C. A., Ross, J. S., Huang, R. S. P., Schrock, A. B., Creeden, J., Fabrizio, D. A., & Tolba, K. A. (2020) · The AAPS Journal · doi:10.1208/s12248-020-00514-4 · Cited by 51 · see citing works
SEOM clinical guidelines for pancreatic and biliary tract cancer (2020)
Gómez‐España, M. A., Montés, A. F., García‐Carbonero, R., Macarulla, T. M., Maurel, J., Martín, Á., Pazo-Cid, R., Vera, R., Carrato, A., & Feliú, J. (2021) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02573-1 · Cited by 45 · see citing works
“Such is the case for pembrolizumab for tumors with microsatellite instability (< 1% of cholangiocarcinomas) or high tumor mutational burden (TMB > 10 mutations/Mb) [53, 54], or TRK-inhibitors (larotrectinib or entrectinib) for tumors with NTRK rearrangements (< 5% of cholangiocarcinomas) [55, 56].”
BackgroundLenci, E., Cantini, L., Pecci, F., Cognigni, V., Agostinelli, V., Mentrasti, G., Lupi, A., Ranallo, N., Paoloni, F., Rinaldi, S., et al. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10051005 · Cited by 45 · see citing works
“In this context, beside tumor tissue biomarkers such as PD-L1 staining, tumor mutational burden (TMB) [26] and immune cells infiltration [27], blood-derived parameters may represent a useful and easy-to-access predictor of immunotherapy response.”
BackgroundBiomarkers in Immunotherapy-Based Precision Treatments of Digestive System Tumors
Zeng, Z., Yang, B., & Liao, Z. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.650481 · Cited by 44 · see citing works
“Meanwhile, different staining platforms are used to test various antibodies; for example, FDA approved Dako 22C3 pharma Dx PD-L1 as a companion diagnostic for pembrolizumab, and Dako 28-8 and Ventana SP142 PD-L1 was approved as complementary diagnostics for nivolumab and atezolizumab, respectively.”
BackgroundInfluentialLelond, S., Ward, J., Lambert, P. J., & Kim, C. (2021) · Current Oncology · doi:10.3390/curroncol28040244 · Cited by 40 · see citing works
“In an assessment of tumor mutational burden (TMB) in KEYNOTE-158 [46], patients with a high TMB also experienced an increased response to immunotherapy.”
BackgroundObesity Is Associated with Altered Tumor Metabolism in Metastatic Melanoma
Hahn, A. W., Menk, A. V., Rivadeneira, D. B., Augustin, R. C., Xu, M., Li, J., Wu, X., Mishra, A. K., Gide, T. N., Quek, C. Y. J., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-2661 · Cited by 37 · see citing works
Pabla, S., Seager, R. J., Roey, E. V., Gao, S., Hoefer, C., Nesline, M., DePietro, P., Burgher, B., Andreas, J., Giamo, V., et al. (2021) · Biomarker Research · doi:10.1186/s40364-021-00308-6 · Cited by 34 · see citing works
“making [13, 15], the complexity of the antitumor host immune response cannot be fully explained by a single biomarker of immune or neoplastic mechanism.”
Backgroundde Kouchkovsky, I., Zhang, L., Philip, E. J., Wright, F., Kim, D. M., Natesan, D., Kwon, D. H.-M., Ho, H., Ho, S., Chan, E., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002127 · Cited by 33 · see citing works
Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors
Morgenstern‐Kaplan, D., Kareff, S. A., Trabolsi, A., Rodríguez, E., Krause, H. B., Ribeiro, J. R., Tan, H., Antonarakis, E. S., Lou, E., Nagasaka, M., et al. (2024) · The Oncologist · doi:10.1093/oncolo/oyae168 · Cited by 31 · see citing works
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Deficient Mismatch Repair and Microsatellite Instability in Solid Tumors
Awosika, J. A., Gulley, J. L., & Pastor, D. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094394 · Cited by 36 · see citing works
“As a result, the existence of the hypermutated phenotype exhibited by dMMR/MSI-H tumors further supports the likelihood of an efficacious response to ICI and favorable outcome [128,131,132].”
Current status of PD-1/PD-L1 blockade immunotherapy in breast cancer
Noguchi, E., Shien, T., & Iwata, H. (2020) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyaa230 · Cited by 30 · see citing works
Galsky, M. D., Balar, A. V., Black, P. C., Campbell, M. T., Dykstra, G., Grivas, P. D., Gupta, S., Hoimes, C. J., López, L., Meeks, J. J., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002552 · Cited by 30 · see citing works
Targeted Therapies and Developing Precision Medicine in Gastric Cancer
Pihlak, R., Fong, C., & Starling, N. (2023) · Cancers · doi:10.3390/cancers15123248 · Cited by 29 · see citing works
Expert opinions on immunotherapy for patients with colorectal cancer
Wang, F., Wang, Z., Chen, G., Luo, H., Zhang, D., Qiu, M., Wang, D., Pan, Z., Shen, L., Li, J., et al. (2020) · 癌症：英文版 · doi:10.1002/cac2.12095 · Cited by 27 · see citing works
“Onemaywonder whether this could be applied to pMMR/MSSmCRC,whichwas not included in the KEYNOTE-158 study [17].”
BackgroundMethodMo, S.-F., Cai, Z.-Z., Kuai, W.-H., Li, X., & Chen, Y. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1209243 · Cited by 25 · see citing works
“As such, our findings firmly support the prespecified TMB cutoff in KEYNOTE-158 (Marabelle et al., 2019; Marabelle et al., 2020) and provide rigorous evidence beyond KEYNOTE-158 for the utility of TMB≥10 mut/Mb as a positive indicator of clinical responses and OS benefits from PD-(L) 1 blockade for a broader range of…”
MethodResultInfluentialIn, G. K., Ribeiro, J. R., Yin, J., Xiu, J., Bustos, M. A., Ito, F., Chow, F. E., Zada, G., Hwang, L., Salama, A. K. S., et al. (2023) · npj Precision Oncology · doi:10.1038/s41698-023-00471-z · Cited by 25 · see citing works
What is the burden of proof for tumor mutational burden in gliomas?
Khasraw, M., Walsh, K. M., Heimberger, A. B., & Ashley, D. M. (2020) · Neuro-Oncology · doi:10.1093/neuonc/noaa256 · Cited by 24 · see citing works
TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors
Krušlin, B., Gatalica, Z., Hes, O., Skenderi, F., Miettinen, M., Contreras, E., Xiu, J., Ellis, M., Florento, E., Vranić, S., et al. (2021) · Clinical Genitourinary Cancer · doi:10.1016/j.clgc.2021.02.002 · Cited by 22 · see citing works
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“High tTMB, defined as ≥ 10 mut/Mb in that study, was not associated with improved survival, although patients with high tTMB were more likely to respond to immunotherapy treatment[15].”
BackgroundPredictive Markers for Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Ushio, R., Murakami, S., & Saito, H. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11071855 · Cited by 20 · see citing works
“In this approval, tTMB-high was defined as having at least 10 mut/Mb according to the KEYNOTE-158 study of pembrolizumab for unresectable or metastatic solid tumors [40].”
MethodPan-Cancer Biomarkers: Changing the Landscape of Molecular Testing
Yao, J., Arcila, M. E., Ladanyi, M., & Hechtman, J. F. (2020) · Archives of Pathology & Laboratory Medicine · doi:10.5858/arpa.2020-0513-ra · Cited by 17 · see citing works
Tarantino, P., Mazzarella, L., Marra, A., Trapani, D., & Curigliano, G. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102169 · Cited by 18 · see citing works
Kelly, A. D., Murugesan, K., Kuang, Z., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003550 · Cited by 17 · see citing works
“12 Despite this, ICI benefits remain restricted to a subset of patients, 13 warranting research into additional predictive biomarkers of checkpoint blockade response.”
The future of tissue-agnostic drugs
Photopoulos, J. (2020) · Nature · doi:10.1038/d41586-020-02679-6 · Cited by 16 · see citing works
Matteucci, L., Bittoni, A., Gallo, G., Ridolfi, L., & Passardi, A. (2023) · Cancers · doi:10.3390/cancers15215189 · Cited by 15 · see citing works
“On the basis of this result, the US FDA approved the use of pembrolizumab for TMB-H solid tumors on 16 June 2020 [157].”
BackgroundAnti-PD-1 elicits regression of undifferentiated pleomorphic sarcomas with UV-mutation signatures
Cheung, L. S., Chen, L., Oke, T. F., Schaffer, T. B., Boudadi, K., Ngo, J. T., Gross, J. M., Kemberling, H., Diaz, L. A., Lipson, E. J., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002345 · Cited by 15 · see citing works
Immunotherapy in small cell lung cancer: one step at a time: a narrative review
Dumoulin, D. W., Dingemans, A. C., Aerts, J. G. J. V., Remón, J., Ruysscher, D. D., & Hendriks, L. E. L. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-630 · Cited by 14 · see citing works
“The RR for patients with higher TMB was 29% (10 out of 34 patients) compared to 10% for patients with low TMB (4 out of 41 patients) (85).”
Huang, Y., Du, Z., Kan, A., He, M., Li, H., Lai, Z., Wen, D., Huang, L., Li, Q., Xu, L., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1260191 · Cited by 14 · see citing works
“Exploratory analysis of prospective trials revealed that higher TMB was associated with superior survival and objective response in advanced solid tumor (36 – 38).”
BackgroundGenomic landscape of diffuse glioma revealed by whole genome sequencing
Kinnersley, B., Jung, J., Cornish, A. J., Chubb, D., Laxton, R. C., Frangou, A., Gruber, A. J., Sud, A., Caravagna, G., Sottoriva, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59156-9 · Cited by 15 · see citing works
“Example therapies for actionable alterations include ivosidenib for oncogenic IDH1 mutations in astrocytomas and oligodendrogliomas 65,66 , PI3K inhibitors in PTEN-de fi cient GBM tumours 67,68 , and pembrolizumab in both TMB-H tumours 69 and MSI-H tumours 70 – 73 (Fig.”
Fang, H., Ma, Q., & Zhong, D. (2022) · Translational Oncology · doi:10.1016/j.tranon.2022.101493 · Cited by 11 · see citing works
Colorectal Cancer Liver Metastasis—State-of-the-Art and Future Perspectives
Ruivo, A. D. S., Oliveira, R. C., Silva-Vaz, P., & Tralhão, J. G. (2023) · Gastrointestinal Disorders · doi:10.3390/gidisord5040046 · Cited by 13 · see citing works
“Results from a KEYNOTE-158 study showed that Pembrolizumab, as an immune checkpoint, is effective in various types of cancers with tumor burden (defined as the number of mutations in cancer cells’ DNA, reported as mutations per megabase) ≥ 10 mut/Mb, particularly solid cancers [106].”
Wessolly, M., Stephan-Falkenau, S., Streubel, A., Wiesweg, M., Borchert, S., Mairinger, E., Kollmeier, J., Reis, H., Bauer, T. T., Schmid, K. W., et al. (2022) · BMC Cancer · doi:10.1186/s12885-021-09111-w · Cited by 12 · see citing works
Predictive Biomarkers for Immune Checkpoint Inhibitors in Advanced Non–Small Cell Lung Cancer
Bhalla, S., Doroshow, D., & Hirsch, F. (2020) · Cancer Journal · doi:10.1097/ppo.0000000000000483 · Cited by 9 · see citing works
Zhou, L. Q., Huang, L., Xu, Q., Lv, Y., Wang, Z., Zhan, P., Han, H., Shao, Y. W., Lin, D., Lv, T., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.596542 · Cited by 10 · see citing works
Keenan, B. P., Loon, K. V., Khilnani, A. D., Fidelman, N. A., Behr, S. C., Atreya, C. E., & Oh, D. Y. (2021) · Anticancer Research · doi:10.21873/anticanres.15080 · Cited by 10 · see citing works
Implementing precision oncology for sarcoma patients: the CCCLMUmolecular tumor board experience
Berclaz, L. M., Burkhard‐Meier, A., Lange, P., Gioia, D. D., Schmidt, M., Knösel, T., Klauschen, F., von Bergwelt‐Baildon, M., Heinemann, V., Greif, P. A., et al. (2023) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-023-05179-y · Cited by 10 · see citing works
“High tumor mutational burden was identified as a predictive parameter for response to immunotherapy in multiple cancer types (Marabelle et al. 2019; Yarchoan et al. 2017).”
BackgroundBiomarker Development for Metastatic Renal Cell Carcinoma: Omics, Antigens, T-cells, and Beyond
Miron, B., Xu, D., & Zibelman, M. R. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10040225 · Cited by 9 · see citing works
“TMB, similarly to MSI, has been investigated independent of tumor histology and has been shown to enrich response to ICB [48,49].”
BackgroundThe efficacy of immune checkpoint inhibitors in thoracic malignancies
Remón, J., Facchinetti, F., & Besse, B. (2021) · European Respiratory Review · doi:10.1183/16000617.0387-2020 · Cited by 9 · see citing works
Key challenges for drugs in clinical development for cholangiocarcinoma
Keenan, B. P., & Kelley, R. K. (2021) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2021.1880565 · Cited by 9 · see citing works
“den (TMB) across tumor types including cholangiocarcinoma, CPI shows much higher rates of response, leading to a tumoragnostic FDA approval for pembrolizumab in tumors of any histology with these features [21,22].”
BackgroundDarabi, S., Elliott, A., Braxton, D. R., et al. (2022) · Cancers · doi:10.3390/cancers14061505 · Cited by 8 · see citing works
“A cutoff point of ≥10 mutations per megabase (mt/MB) was used based on the KEYNOTE-158 pembrolizumab trial [14].”
MethodPan-Cancer Molecular Biomarkers
Dong, F. (2021) · Surgical pathology clinics · doi:10.1016/j.path.2021.05.012 · Cited by 8 · see citing works
Tostes, F. T., Fernandes, Í., Segatelli, V., Callegaro, D., & Pestana, R. C. (2021) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2021.05.008 · Cited by 7 · see citing works
Queiroz, M. M., de Souza, Z. S., Gongora, A. B. L., Barbosa, F. D. G., Buchpiguel, C. A., de Castro, M. G., de Macêdo, M. P., Coelho, R. F., Sokol, E. S., Camargo, A. A., et al. (2021) · ecancermedicalscience · doi:10.3332/ecancer.2021.1306 · Cited by 7 · see citing works
Integrating Precision Medicine into the Contemporary Management of Gynecologic Cancers
Wolford, J. E., Ferrigni, E. N., Margul, D. J., & Herzog, T. J. (2022) · Current Oncology Reports · doi:10.1007/s11912-021-01163-2 · Cited by 8 · see citing works
Advances and Therapeutic Perspectives in Extended-Stage Small-Cell Lung Cancer
Pierret, T., Toffart, A., Levra, M. G., Moro‐Sibilot, D., & Gobbini, É. (2020) · Cancers · doi:10.3390/cancers12113224 · Cited by 6 · see citing works
Brasó‐Maristany, F., Sansó, M., Chic, N., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.710596 · Cited by 7 · see citing works
“, TMB (3, 14) and mismatch repair deficiency (15).”
BackgroundTreating Colorectal Cancer with Immunotherapy: Implications for Single Versus Combination Therapy
Karki, S., Umar, S., & Kasi, A. (2020) · Current Colorectal Cancer Reports · doi:10.1007/s11888-020-00459-y · Cited by 6 · see citing works
Immune Checkpoint Inhibitor Therapy in Colorectal Cancer—The Role of Cellular Pathology
Bateman, A. C. (2021) · International Journal of Surgical Pathology · doi:10.1177/10668969211025844 · Cited by 6 · see citing works
“TMB may be measured directly, where a high level of mutational burden has been defined as the presence of 10 or more mutations per megabase (Mb—1 Mb is 1 000 000 DNA base pairs).(16) However, surrogate measures of TMB are easier to perform in a routine clinical setting and the most important of these is the presence o…”
BackgroundMcLean, L. S., Lim, A., Angel, C., Young, R., Pizzolla, A., Archer, S., Solomon, B., Thai, A., Lewin, J., & Rischin, D. (2024) · Cancers · doi:10.3390/cancers16081452 · Cited by 4 · see citing works
“TMB has also been shown to be a predictive marker of ICI responses in other cancers [50] and was uniformly elevated in all of our cases.”
ResultBreaking Through: Immunotherapy Innovations in Pleural Mesothelioma
Sofianidi, A. A., Syrigos, N. K., Blyth, K. G., Charpidou, A. G., & Vathiotis, I. A. (2025) · Clinical Lung Cancer · doi:10.1016/j.cllc.2025.04.008 · Cited by 5 · see citing works
Harnessing Biomarkers of Response to Improve Therapy Selection in Esophago-Gastric Adenocarcinoma
Fong, C., & Chau, I. (2021) · Pharmacogenomics · doi:10.2217/pgs-2020-0090 · Cited by 4 · see citing works
Malignant struma ovarii with late recurrence harbouring high microsatellite instability
Chung, S. Y., Chi, J., Park, J., et al. (2021) · BMJ Case Reports · doi:10.1136/bcr-2021-242081 · Cited by 4 · see citing works
Deshmukh, R., Verma, S., Yaduwanshi, P. S., Dubey, A., & Kumari, M. (2025) · Current Cancer Drug Targets · doi:10.2174/0115680096333058241114064802 · Cited by 5 · see citing works
Personalized Medicine in Oncology
Vanderwalde, A. M. (2022) · MDPI eBooks · doi:10.3390/books978-3-0365-2820-5 · Cited by 4 · see citing works
Agostini, M., Traldi, P., & Hamdan, M. H. (2025) · Journal of Personalized Medicine · doi:10.3390/jpm15120596 · Cited by 2 · see citing works
“This trial reported that patients with previously treated, unresectable or metastatic solid tumors, having TMB-high status ( 10 mutations per mega base), showed a clinically meaningful improvement in the efficacy of pembrolizumab against PD-1 check-points [46].”
Radovich, M., Wacker, J. W., Solzak, J. P., Tae, H., Ribeiro, J. R., Maney, T., Hancock, B. A., Hamrick, J., Sledge, G. W., Ahluwalia, M., et al. (2026) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-026-04365-4 · Cited by 2 · see citing works
“…indications across both solid and liquid tumors [14], including a tissue-agnostic approval in 2020 for the treatment of unresectable or metastatic solid tumors with TMB ≥ 10 mutations/megabase (mut/Mb) that have progressed on prior therapy [15–17], detected using an FDA-approved test [16–20].”
Loose Regulatory Standards Portend a New Era of Imprecision Oncology
Khaki, A. R. (2020) · Cancer Investigation · doi:10.1080/07357907.2020.1851705 · Cited by 2 · see citing works
Mismatch repair proteins expression and tumor‑infiltrating T‑cells in colorectal cancer
Shigaki, T., Fujiyoshi, K., Sudo, T., Kawahara, A., NAKANE, H., Yomoda, T., Nagasu, S., Kinugasa, T., Akiba, J., Fujita, F., et al. (2022) · Oncology Letters · doi:10.3892/ol.2022.13516 · Cited by 2 · see citing works
“However, the results were similar to those of large‐scale trials (40,41), supporting the accuracy of the findings.”
ResultNew methodology of TMB assessment from tissue and liquid biopsy in NSCLC
Křížová, Ľ., Šafaříková, M., Kalousová, M., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0275121 · Cited by 2 · see citing works
“The study did not show any increase in median PFS, but after more than four months of therapy, atezolizumab showed a significant improvement in PFS [41].”
BackgroundInfluentialShukla, P. D., Nguyen, M. P., Lui, A., Catalan, T., Young, J. S., Berger, M. S., Theodosopoulos, P. V., Hervey‐Jumper, S. L., Huppert, L. A., Aghi, M. K., et al. (2025) · Journal of neurosurgery · doi:10.3171/2024.9.jns241391 · Cited by 2 · see citing works
Deng, X., Ablise, M., Xiamuxi, H., Yan, T., Imam, M., Wang, Y., Zu, M., & Wumaier, W. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1715712 · Cited by 2 · see citing works
“…therapies, including surgery, radiotherapy, and platinum-based chemotherapy, are often limited by high tumor drug resistance and their own toxicity (Marabelle et al., 2020), leading to tumor recurrence in approximately 40% of patients with advanced cervical cancer within 5 years (Liontos et al.,…”
Systemic Treatments of Castration-Resistant Prostate Cancer
Desai, A. N., Fleyshman, M., Lall, N., & Saraiya, B. (2026) · Urologic Clinics of North America · doi:10.1016/j.ucl.2026.02.013 · Cited by 1 · see citing works
Pan-Cancer Molecular Biomarkers
Dong, F. (2024) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2023.08.013 · Cited by 3 · see citing works
Raez, L. E., Baca, Y., Ribeiro, J. R., Nieva, J. J., Mamdani, H. M., Junior, G. L. L., Borghaei, H., Socinski, M. A., Wozniak, A. J., Vanderwalde, A. M., et al. (2025) · Expert Review of Anticancer Therapy · doi:10.1080/14737140.2025.2491648 · Cited by 1 · see citing works
“A cutoff point of ≥ 10 mutations per mega-base (Mb) was used based on the KEYNOTE-158 pembrolizu-mab trial [23].”
Immunotherapy in Pancreatic Cancer
El‐Rayes, B. F., & Akce, M. (2020) · Digestive Disease Interventions · doi:10.1055/s-0040-1718904 · Cited by 2 · see citing works
Expanding the Role of Checkpoint Inhibitors in Immune Cold Tumors
Acuña-Villaorduña, A., Gali, R., Chergui, A., & Goel, S. (2021) · Advances in Oncology · doi:10.1016/j.yao.2021.02.008
Perspective on the Immunotherapy of Pancreatic Cancer
Keenan, B. P., & Tempero, M. A. (2021) · Cancer immunotherapy · doi:10.1007/13905_2021_9
Anaplastic Thyroid Carcinoma, Thyroid Lymphoma, and Metastases
Moyer, K. F., Wong, R. J., & Shaha, A. R. (2021) · Springer eBooks · doi:10.1007/978-3-030-84737-1_9
Authors, V. (2013) · Current Oncology · doi:10.3747/co.20.1906
Dişel, U., Köse, F., Bilici, A. E., et al. (2022) · Journal of Oncological Sciences · doi:10.37047/jos.2022-89310
Radiotherapy and Immunotherapy for Head and Neck Cancer
Qian, J. M., & Schoenfeld, J. D. (2022) · Springer eBooks · doi:10.1007/978-3-031-05973-5_7
Pedersen, K. S., Foster, N. R., Overman, M. J., et al. (2023) · doi:10.1158/1078-0432.c.6530637
Self-citationPedersen, K. S., Foster, N. R., Overman, M. J., et al. (2023) · doi:10.1158/1078-0432.c.6530637.v1
Self-citation
- Authors
- Marabelle, A., Fakih, M. G., Lopez, J., Shah, M., Shapira-Frommer, R., Nakagawa, K., Chung, H. C., Kindler, H. L., Lopez-Martin, J. A., Miller, W., Italiano, A., Kao, S., Piha-Paul, S. A., Delord, J.-P., McWilliams, R. R., Aurora-Garg, D., Chen, M., Jin, F., Norwood, K., & Bang, Y.-J.
- Affiliations
- Inserm (FR)
- City Of Hope National Medical Center (US)
- Royal Marsden NHS Foundation Trust (GB)
- The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
- Kindai University (JP)
- Yonsei University (KR)
- University of Chicago (US)
- Research Institute Hospital 12 de Octubre (ES)
- Jewish General Hospital (CA)
- Institut Bergonié (FR)
- Chris O’Brien Lifehouse (AU)
- The University of Texas MD Anderson Cancer Center (US)
- Institut universitaire du cancer de Toulouse Oncopole (FR)
- Mayo Clinic (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Seoul National University (KR)
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 30
- Pages
- v477-v478
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2978458313
- Cited by
- 104
- References
- 0
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 14 · 2021: 35 · 2020: 27 · 2013: 1
- FWCI
- 7.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- tumor mutational burden, pembrolizumab, immune checkpoint inhibitors, advanced solid tumors, predictive biomarkers, treatment outcomes, KEYNOTE-158, melanoma, non-small cell lung cancer
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