A Panel-Based Mutational Signature of Mismatch Repair Deficiency is Associated With Durable Response to Pembrolizumab in Metastatic Castration-Resistant Prostate Cancer
Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pemb...
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Published in | Clinical genitourinary cancer Vol. 22; no. 2; pp. 558 - 568.e3 |
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Elsevier Inc
01.04.2024
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Abstract | Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab.
Clinico-genomic data was obtained for 2664 patients with PCa sequenced at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering (MSK). Clinical outcomes were collected for patients with metastatic castration-resistant PCa (mCRPC) treated with pembrolizumab at DFCI. SigMA was used to characterize tumors as MMRd or MMR proficient (MMRp). The concordance between MMRd with microsatellite instability (MSI-H) was assessed. Radiographic progression-free survival (rPFS) and overall survival (OS) were collected for patients treated with pembrolizumab. Event-time distributions were estimated using Kaplan-Meier methodology.
Across both cohorts, 100% (DFCI: 12/12; MSK: 43/43) of MSI-H tumors were MMRd. However, 14% (2/14) and 9.1% (6/66) of MMRd tumors in the DFCI and MSK cohorts respectively were microsatellite stable (MSS), and 26% (17/66) were MSI-indeterminate in the MSK cohort. Among patients treated with pembrolizumab, those with MMRd (n = 5) versus MMRp (n = 14) mCRPC experienced markedly improved rPFS (HR = 0.088, 95% CI: 0.011-0.70; P = .0064) and OS (HR = 0.11, 95% CI: 0.014-0.80; P = .010) from start of treatment. Four patients with MMRd experienced remissions of >= 2.5 years.
SigMA detects additional cases of MMRd as compared to MSI testing in PCa and identifies patients likely to experience durable response to pembrolizumab.
Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa) and better biomarkers are needed to predict responses to ICIs. In this study, we found that SigMA detects additional cases of mismatch repair deficiency as compared to microsatellite testing in PCa and identifies patients likely to experience durable response to pembrolizumab. |
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AbstractList | Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab.
Clinico-genomic data was obtained for 2664 patients with PCa sequenced at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering (MSK). Clinical outcomes were collected for patients with metastatic castration-resistant PCa (mCRPC) treated with pembrolizumab at DFCI. SigMA was used to characterize tumors as MMRd or MMR proficient (MMRp). The concordance between MMRd with microsatellite instability (MSI-H) was assessed. Radiographic progression-free survival (rPFS) and overall survival (OS) were collected for patients treated with pembrolizumab. Event-time distributions were estimated using Kaplan-Meier methodology.
Across both cohorts, 100% (DFCI: 12/12; MSK: 43/43) of MSI-H tumors were MMRd. However, 14% (2/14) and 9.1% (6/66) of MMRd tumors in the DFCI and MSK cohorts respectively were microsatellite stable (MSS), and 26% (17/66) were MSI-indeterminate in the MSK cohort. Among patients treated with pembrolizumab, those with MMRd (n = 5) versus MMRp (n = 14) mCRPC experienced markedly improved rPFS (HR = 0.088, 95% CI: 0.011-0.70; P = .0064) and OS (HR = 0.11, 95% CI: 0.014-0.80; P = .010) from start of treatment. Four patients with MMRd experienced remissions of >= 2.5 years.
SigMA detects additional cases of MMRd as compared to MSI testing in PCa and identifies patients likely to experience durable response to pembrolizumab. Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab. Clinico-genomic data was obtained for 2664 patients with PCa sequenced at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering (MSK). Clinical outcomes were collected for patients with metastatic castration-resistant PCa (mCRPC) treated with pembrolizumab at DFCI. SigMA was used to characterize tumors as MMRd or MMR proficient (MMRp). The concordance between MMRd with microsatellite instability (MSI-H) was assessed. Radiographic progression-free survival (rPFS) and overall survival (OS) were collected for patients treated with pembrolizumab. Event-time distributions were estimated using Kaplan-Meier methodology. Across both cohorts, 100% (DFCI: 12/12; MSK: 43/43) of MSI-H tumors were MMRd. However, 14% (2/14) and 9.1% (6/66) of MMRd tumors in the DFCI and MSK cohorts respectively were microsatellite stable (MSS), and 26% (17/66) were MSI-indeterminate in the MSK cohort. Among patients treated with pembrolizumab, those with MMRd (n = 5) versus MMRp (n = 14) mCRPC experienced markedly improved rPFS (HR = 0.088, 95% CI: 0.011-0.70; P = .0064) and OS (HR = 0.11, 95% CI: 0.014-0.80; P = .010) from start of treatment. Four patients with MMRd experienced remissions of >= 2.5 years. SigMA detects additional cases of MMRd as compared to MSI testing in PCa and identifies patients likely to experience durable response to pembrolizumab. Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa) and better biomarkers are needed to predict responses to ICIs. In this study, we found that SigMA detects additional cases of mismatch repair deficiency as compared to microsatellite testing in PCa and identifies patients likely to experience durable response to pembrolizumab. INTRODUCTION/BACKGROUNDImmune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab.PATIENTS AND METHODSClinico-genomic data was obtained for 2664 patients with PCa sequenced at Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering (MSK). Clinical outcomes were collected for patients with metastatic castration-resistant PCa (mCRPC) treated with pembrolizumab at DFCI. SigMA was used to characterize tumors as MMRd or MMR proficient (MMRp). The concordance between MMRd with microsatellite instability (MSI-H) was assessed. Radiographic progression-free survival (rPFS) and overall survival (OS) were collected for patients treated with pembrolizumab. Event-time distributions were estimated using Kaplan-Meier methodology.RESULTSAcross both cohorts, 100% (DFCI: 12/12; MSK: 43/43) of MSI-H tumors were MMRd. However, 14% (2/14) and 9.1% (6/66) of MMRd tumors in the DFCI and MSK cohorts respectively were microsatellite stable (MSS), and 26% (17/66) were MSI-indeterminate in the MSK cohort. Among patients treated with pembrolizumab, those with MMRd (n = 5) versus MMRp (n = 14) mCRPC experienced markedly improved rPFS (HR = 0.088, 95% CI: 0.011-0.70; P = .0064) and OS (HR = 0.11, 95% CI: 0.014-0.80; P = .010) from start of treatment. Four patients with MMRd experienced remissions of >= 2.5 years.CONCLUSIONSigMA detects additional cases of MMRd as compared to MSI testing in PCa and identifies patients likely to experience durable response to pembrolizumab. |
Author | Lakshminarayanan, Gitanjali Sholl, Lynette M. Ananda, Guruprasad Silver, Rebecca Berchuck, Jacob E. Gulhan, Doga C. Boiarsky, Daniel Hirsch, Michelle S. Park, Peter J. Savignano, Hunter Choudhury, Atish D. Tewari, Alok K. McClure, Heather M. |
Author_xml | – sequence: 1 givenname: Daniel orcidid: 0009-0007-5740-9244 surname: Boiarsky fullname: Boiarsky, Daniel organization: Department of Medicine, Tufts Medical Center, Boston, MA – sequence: 2 givenname: Doga C. surname: Gulhan fullname: Gulhan, Doga C. organization: Department of Biomedical Informatics, Harvard Medical School, Boston, MA – sequence: 3 givenname: Hunter surname: Savignano fullname: Savignano, Hunter organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA – sequence: 4 givenname: Gitanjali surname: Lakshminarayanan fullname: Lakshminarayanan, Gitanjali organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA – sequence: 5 givenname: Heather M. surname: McClure fullname: McClure, Heather M. organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA – sequence: 6 givenname: Rebecca orcidid: 0000-0003-3730-2144 surname: Silver fullname: Silver, Rebecca organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA – sequence: 7 givenname: Michelle S. surname: Hirsch fullname: Hirsch, Michelle S. organization: Department of Pathology, Brigham and Women's Hospital, Boston, MA – sequence: 8 givenname: Lynette M. surname: Sholl fullname: Sholl, Lynette M. organization: Department of Pathology, Brigham and Women's Hospital, Boston, MA – sequence: 9 givenname: Atish D. orcidid: 0000-0001-9344-6631 surname: Choudhury fullname: Choudhury, Atish D. organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA – sequence: 10 givenname: Guruprasad orcidid: 0000-0001-6697-3479 surname: Ananda fullname: Ananda, Guruprasad organization: Department of Data Science, Dana-Farber Cancer Institute, Boston, MA – sequence: 11 givenname: Peter J. surname: Park fullname: Park, Peter J. organization: Department of Biomedical Informatics, Harvard Medical School, Boston, MA – sequence: 12 givenname: Alok K. surname: Tewari fullname: Tewari, Alok K. organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA – sequence: 13 givenname: Jacob E. surname: Berchuck fullname: Berchuck, Jacob E. email: jacob_berchuck@dfci.harvard.edu organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA |
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Cites_doi | 10.1016/j.esmoop.2021.100120 10.1038/s41588-019-0390-2 10.3389/fonc.2022.969238 10.1200/JCO.2016.69.1584 10.1200/PO.20.00185 10.1371/journal.pone.0233260 10.1093/annonc/mdz116 10.1001/jamaoncol.2018.5801 10.1038/s43018-021-00200-0 10.1158/2159-8290.CD-21-0007 10.1093/bioinformatics/btt755 10.1002/onco.13601 10.1136/jitc-2020-001065 10.1016/S1470-2045(14)70189-5 10.1200/JCO.18.00283 10.1053/j.gastro.2021.05.007 10.1016/j.cell.2022.01.003 10.1016/j.cell.2015.05.001 10.1200/JCO.2015.64.2702 10.1016/j.eururo.2018.10.009 10.1038/s41586-020-1943-3 10.1038/nm.4292 10.1200/JCO.19.01638 10.1200/JCO.19.02105 10.1200/JCO.2021.39.6_suppl.98 10.5858/arpa.2016-0527-OA 10.1016/S0092-8674(00)80433-X 10.1016/j.ccell.2020.08.007 10.1111/his.14645 10.1001/jamaoncol.2018.4942 10.1001/jamaoncol.2019.2187 10.1158/1078-0432.CCR-21-3045 10.1002/ijc.33115 |
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Keywords | Pembrolizumab Immune checkpoint inhibitors Mismatch repair deficiency Genomic signature |
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References | Abida, Cheng, Armenia (bib0007) 2019; 5 Luchini, Bibeau, Ligtenberg (bib0020) 2019; 30 Sena, Fountain, Isaacsson (bib0011) 2021; 26 Choudhury, Kwak, Cheung (bib0034) 2021; 39 Antonarakis, Piulats, Gross-Goupil (bib0002) 2020; 38 Graham, Montgomery, Cheng (bib0010) 2020; 15 Edelmann, Yang, Umar (bib0037) 1997; 91 Barata, Agarwal, Nussenzveig (bib0013) 2020; 8 Ratovomanana, Cohen, Svrcek (bib0015) 2021; 161 Sharma, Pachynski, Narayan (bib0005) 2020; 38 Färkkilä, Gulhan, Casado (bib0023) 2020; 11 National Comprehensive Cancer Network. Prostate cancer (version 1.2023). Accessed: July 1, 2023. Available at Batalini, Xiong, Tayob (bib0022) 2022; 28 Latham, Srinivasan, Kemel (bib0008) 2019; 37 Gulhan, Lee, Melloni, Cortés-Ciriano, Park (bib0025) 2019; 51 Scher, Morris, Stadler (bib0031) 2016; 34 Gulhan DC, Viswanadham V, Mutas F, et al. Predicting response to immune checkpoint blockade therapy among mismatch repair-deficient patients using mutational signatures. medRxiv Marabelle, Le, Ascierto (bib0009) 2020; 38 Cohen, Hain, Buhard (bib0016) 2019; 5 Alexandrov, Kim, Haradhvala (bib0026) 2020; 578 Albayrak, Garrido-Castro, Giannakis (bib0033) 2020; 4 Topalian, Hodi, Brahmer (bib0001) 2019; 5 Beer, Kwon, Drake (bib0004) 2017; 35 Niu, Ye, Zhang (bib0032) 2014; 30 Antonarakis, Shaukat, Isaacsson (bib0012) 2019; 75 Nguyen, Fong, Luthra (bib0030) 2022; 185 Carreira, Porta, Arce-Gallego (bib0035) 2021; 11 Kwon, Drake, Scher (bib0003) 2014; 15 . Yakushina, Kavun, Veselovsky (bib0014) 2023; 7 Salem, Bodor, Puccini (bib0036) 2020; 147 Davies, Glodzik, Morganella (bib0024) 2017; 23 Guyot D'Asnières De Salins, Tachon, Cohen (bib0017) 2021; 6 Garcia, Minkovsky, Jia (bib0029) 2017; 141 Zou, Koh, Nanda (bib0027) 2021; 2 Wyvekens, Tsai, Sholl (bib0018) 2022; 80 Marques, Ferraro-Peyret, Michaud (bib0021) 2022; 12 Robinson, Van Allen, Wu (bib0006) 2015; 161 Robinson (10.1016/j.clgc.2024.01.011_bib0006) 2015; 161 Niu (10.1016/j.clgc.2024.01.011_bib0032) 2014; 30 Abida (10.1016/j.clgc.2024.01.011_bib0007) 2019; 5 Yakushina (10.1016/j.clgc.2024.01.011_bib0014) 2023; 7 Nguyen (10.1016/j.clgc.2024.01.011_bib0030) 2022; 185 Luchini (10.1016/j.clgc.2024.01.011_bib0020) 2019; 30 Batalini (10.1016/j.clgc.2024.01.011_bib0022) 2022; 28 Davies (10.1016/j.clgc.2024.01.011_bib0024) 2017; 23 Sharma (10.1016/j.clgc.2024.01.011_bib0005) 2020; 38 10.1016/j.clgc.2024.01.011_bib0019 Garcia (10.1016/j.clgc.2024.01.011_bib0029) 2017; 141 Choudhury (10.1016/j.clgc.2024.01.011_bib0034) 2021; 39 Beer (10.1016/j.clgc.2024.01.011_bib0004) 2017; 35 Marabelle (10.1016/j.clgc.2024.01.011_bib0009) 2020; 38 Antonarakis (10.1016/j.clgc.2024.01.011_bib0012) 2019; 75 Ratovomanana (10.1016/j.clgc.2024.01.011_bib0015) 2021; 161 Färkkilä (10.1016/j.clgc.2024.01.011_bib0023) 2020; 11 Zou (10.1016/j.clgc.2024.01.011_bib0027) 2021; 2 Gulhan (10.1016/j.clgc.2024.01.011_bib0025) 2019; 51 Scher (10.1016/j.clgc.2024.01.011_bib0031) 2016; 34 Guyot D'Asnières De Salins (10.1016/j.clgc.2024.01.011_bib0017) 2021; 6 Kwon (10.1016/j.clgc.2024.01.011_bib0003) 2014; 15 Sena (10.1016/j.clgc.2024.01.011_bib0011) 2021; 26 Antonarakis (10.1016/j.clgc.2024.01.011_bib0002) 2020; 38 Graham (10.1016/j.clgc.2024.01.011_bib0010) 2020; 15 Albayrak (10.1016/j.clgc.2024.01.011_bib0033) 2020; 4 Carreira (10.1016/j.clgc.2024.01.011_bib0035) 2021; 11 Edelmann (10.1016/j.clgc.2024.01.011_bib0037) 1997; 91 Latham (10.1016/j.clgc.2024.01.011_bib0008) 2019; 37 Marques (10.1016/j.clgc.2024.01.011_bib0021) 2022; 12 Wyvekens (10.1016/j.clgc.2024.01.011_bib0018) 2022; 80 Cohen (10.1016/j.clgc.2024.01.011_bib0016) 2019; 5 Barata (10.1016/j.clgc.2024.01.011_bib0013) 2020; 8 Topalian (10.1016/j.clgc.2024.01.011_bib0001) 2019; 5 10.1016/j.clgc.2024.01.011_bib0028 Alexandrov (10.1016/j.clgc.2024.01.011_bib0026) 2020; 578 Salem (10.1016/j.clgc.2024.01.011_bib0036) 2020; 147 |
References_xml | – volume: 5 start-page: 1411 year: 2019 end-page: 1420 ident: bib0001 article-title: Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab publication-title: JAMA Oncol contributor: fullname: Brahmer – volume: 11 start-page: 1 year: 2020 end-page: 13 ident: bib0023 article-title: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer publication-title: Nat Commun contributor: fullname: Casado – volume: 51 start-page: 912 year: 2019 end-page: 919 ident: bib0025 article-title: Detecting the mutational signature of homologous recombination deficiency in clinical samples publication-title: Nat Genet contributor: fullname: Park – volume: 4 start-page: 1084 year: 2020 end-page: 1097 ident: bib0033 article-title: Clinical pan-cancer assessment of mismatch repair deficiency using tumor-only, targeted next-generation sequencing publication-title: JCO Precis Oncol contributor: fullname: Giannakis – volume: 15 start-page: 1 year: 2020 end-page: 11 ident: bib0010 article-title: Mismatch repair deficiency in metastatic prostate cancer: response to PD-1 blockade and standard therapies publication-title: PLoS One contributor: fullname: Cheng – volume: 15 start-page: 700 year: 2014 end-page: 712 ident: bib0003 article-title: Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial publication-title: Lancet Oncol contributor: fullname: Scher – volume: 5 start-page: 471 year: 2019 end-page: 478 ident: bib0007 article-title: Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade publication-title: JAMA Oncol contributor: fullname: Armenia – volume: 38 start-page: 395 year: 2020 end-page: 405 ident: bib0002 article-title: Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase II KEYNOTE-199 study publication-title: J Clin Oncol contributor: fullname: Gross-Goupil – volume: 578 start-page: 94 year: 2020 end-page: 101 ident: bib0026 article-title: The repertoire of mutational signatures in human cancer publication-title: Nature contributor: fullname: Haradhvala – volume: 11 start-page: 2812 year: 2021 end-page: 2827 ident: bib0035 article-title: Biomarkers associating with PARP inhibitor benefit in prostate cancer in the TOPARP-B trial publication-title: Cancer Discov contributor: fullname: Arce-Gallego – volume: 35 start-page: 40 year: 2017 end-page: 47 ident: bib0004 article-title: Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer publication-title: J Clin Oncol contributor: fullname: Drake – volume: 75 start-page: 378 year: 2019 end-page: 382 ident: bib0012 article-title: Clinical features and therapeutic outcomes in men with advanced prostate cancer and DNA mismatch repair gene mutations publication-title: Eur Urol contributor: fullname: Isaacsson – volume: 30 start-page: 1015 year: 2014 ident: bib0032 article-title: MSIsensor: microsatellite instability detection using paired tumor-normal sequence data publication-title: Bioinformatics contributor: fullname: Zhang – volume: 185 start-page: 563 year: 2022 end-page: 575.e11 ident: bib0030 article-title: Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients publication-title: Cell contributor: fullname: Luthra – volume: 38 start-page: 489 year: 2020 end-page: 499 ident: bib0005 article-title: Nivolumab plus ipilimumab for metastatic castration-resistant prostate cancer: preliminary analysis of patients in the CheckMate 650 trial publication-title: Cancer Cell contributor: fullname: Narayan – volume: 5 start-page: 551 year: 2019 end-page: 555 ident: bib0016 article-title: Association of primary resistance to immune checkpoint inhibitors in metastatic colorectal cancer with misdiagnosis of microsatellite instability or mismatch repair deficiency status publication-title: JAMA Oncol contributor: fullname: Buhard – volume: 12 start-page: 1 year: 2022 end-page: 12 ident: bib0021 article-title: Improved NGS-based detection of microsatellite instability using tumor-only data publication-title: Front Oncol contributor: fullname: Michaud – volume: 91 start-page: 467 year: 1997 end-page: 477 ident: bib0037 article-title: Mutation in the mismatch repair gene Msh6 causes cancer susceptibility publication-title: Cell contributor: fullname: Umar – volume: 39 start-page: 98 year: 2021 ident: bib0034 article-title: Randomized phase II study evaluating the addition of pembrolizumab to radium-223 in metastatic castration-resistant prostate cancer publication-title: J Clin Oncol contributor: fullname: Cheung – volume: 37 start-page: 286 year: 2019 end-page: 295 ident: bib0008 article-title: Microsatellite instability is associated with the presence of lynch syndrome pan-cancer publication-title: J Clin Oncol contributor: fullname: Kemel – volume: 8 start-page: 1 year: 2020 end-page: 5 ident: bib0013 article-title: Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA publication-title: J Immunother Cancer contributor: fullname: Nussenzveig – volume: 80 start-page: 1050 year: 2022 end-page: 1060 ident: bib0018 article-title: Histopathological and genetic features of mismatch repair-deficient high-grade prostate cancer publication-title: Histopathology contributor: fullname: Sholl – volume: 23 start-page: 517 year: 2017 end-page: 525 ident: bib0024 article-title: HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures publication-title: Nat Med contributor: fullname: Morganella – volume: 34 start-page: 1402 year: 2016 end-page: 1418 ident: bib0031 article-title: Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3 publication-title: J Clin Oncol contributor: fullname: Stadler – volume: 28 start-page: 1493 year: 2022 end-page: 1499 ident: bib0022 article-title: Phase 1b clinical trial with alpelisib plus olaparib for patients with advanced triple-negative breast cancer publication-title: Clin Cancer Res contributor: fullname: Tayob – volume: 147 start-page: 2948 year: 2020 end-page: 2956 ident: bib0036 article-title: Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors publication-title: Int J Cancer contributor: fullname: Puccini – volume: 2 start-page: 643 year: 2021 end-page: 657 ident: bib0027 article-title: A systematic CRISPR screen defines mutational mechanisms underpinning signatures caused by replication errors and endogenous DNA damage publication-title: Nature cancer contributor: fullname: Nanda – volume: 141 start-page: 751 year: 2017 end-page: 758 ident: bib0029 article-title: Validation of OncoPanel: a targeted next-generation sequencing assay for the detection of somatic variants in cancer publication-title: Arch Pathol Lab Med contributor: fullname: Jia – volume: 6 year: 2021 ident: bib0017 article-title: Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer publication-title: ESMO Open contributor: fullname: Cohen – volume: 38 start-page: 1 year: 2020 ident: bib0009 article-title: Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair–deficient cancer: results from the phase II KEYNOTE-158 study publication-title: J Clin Oncol contributor: fullname: Ascierto – volume: 26 start-page: 270 year: 2021 end-page: 278 ident: bib0011 article-title: Tumor frameshift mutation proportion predicts response to immunotherapy in mismatch repair-deficient prostate cancer publication-title: Oncologist contributor: fullname: Isaacsson – volume: 161 start-page: 1215 year: 2015 end-page: 1218 ident: bib0006 article-title: Integrative clinical genomics of advanced prostate cancer publication-title: Cell contributor: fullname: Wu – volume: 7 year: 2023 ident: bib0014 article-title: Microsatellite instability detection: the current standards, limitations, and misinterpretations publication-title: JCO Precis Oncol contributor: fullname: Veselovsky – volume: 161 start-page: 814 year: 2021 end-page: 826.e7 ident: bib0015 article-title: Performance of next-generation sequencing for the detection of microsatellite instability in colorectal cancer with deficient DNA mismatch repair publication-title: Gastroenterology contributor: fullname: Svrcek – volume: 30 start-page: 1232 year: 2019 end-page: 1243 ident: bib0020 article-title: ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach publication-title: Ann Oncol contributor: fullname: Ligtenberg – volume: 7 year: 2023 ident: 10.1016/j.clgc.2024.01.011_bib0014 article-title: Microsatellite instability detection: the current standards, limitations, and misinterpretations publication-title: JCO Precis Oncol contributor: fullname: Yakushina – volume: 6 issue: 3 year: 2021 ident: 10.1016/j.clgc.2024.01.011_bib0017 article-title: Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer publication-title: ESMO Open doi: 10.1016/j.esmoop.2021.100120 contributor: fullname: Guyot D'Asnières De Salins – volume: 51 start-page: 912 issue: 5 year: 2019 ident: 10.1016/j.clgc.2024.01.011_bib0025 article-title: Detecting the mutational signature of homologous recombination deficiency in clinical samples publication-title: Nat Genet doi: 10.1038/s41588-019-0390-2 contributor: fullname: Gulhan – volume: 12 start-page: 1 year: 2022 ident: 10.1016/j.clgc.2024.01.011_bib0021 article-title: Improved NGS-based detection of microsatellite instability using tumor-only data publication-title: Front Oncol doi: 10.3389/fonc.2022.969238 contributor: fullname: Marques – volume: 35 start-page: 40 issue: 1 year: 2017 ident: 10.1016/j.clgc.2024.01.011_bib0004 article-title: Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2016.69.1584 contributor: fullname: Beer – volume: 4 start-page: 1084 issue: 4 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0033 article-title: Clinical pan-cancer assessment of mismatch repair deficiency using tumor-only, targeted next-generation sequencing publication-title: JCO Precis Oncol doi: 10.1200/PO.20.00185 contributor: fullname: Albayrak – volume: 11 start-page: 1 issue: 1 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0023 article-title: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer publication-title: Nat Commun contributor: fullname: Färkkilä – ident: 10.1016/j.clgc.2024.01.011_bib0028 – volume: 15 start-page: 1 issue: 5 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0010 article-title: Mismatch repair deficiency in metastatic prostate cancer: response to PD-1 blockade and standard therapies publication-title: PLoS One doi: 10.1371/journal.pone.0233260 contributor: fullname: Graham – volume: 30 start-page: 1232 issue: 8 year: 2019 ident: 10.1016/j.clgc.2024.01.011_bib0020 article-title: ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach publication-title: Ann Oncol doi: 10.1093/annonc/mdz116 contributor: fullname: Luchini – volume: 5 start-page: 471 issue: 4 year: 2019 ident: 10.1016/j.clgc.2024.01.011_bib0007 article-title: Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade publication-title: JAMA Oncol doi: 10.1001/jamaoncol.2018.5801 contributor: fullname: Abida – volume: 2 start-page: 643 issue: 6 year: 2021 ident: 10.1016/j.clgc.2024.01.011_bib0027 article-title: A systematic CRISPR screen defines mutational mechanisms underpinning signatures caused by replication errors and endogenous DNA damage publication-title: Nature cancer doi: 10.1038/s43018-021-00200-0 contributor: fullname: Zou – volume: 11 start-page: 2812 issue: 11 year: 2021 ident: 10.1016/j.clgc.2024.01.011_bib0035 article-title: Biomarkers associating with PARP inhibitor benefit in prostate cancer in the TOPARP-B trial publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-21-0007 contributor: fullname: Carreira – volume: 30 start-page: 1015 issue: 7 year: 2014 ident: 10.1016/j.clgc.2024.01.011_bib0032 article-title: MSIsensor: microsatellite instability detection using paired tumor-normal sequence data publication-title: Bioinformatics doi: 10.1093/bioinformatics/btt755 contributor: fullname: Niu – volume: 26 start-page: 270 issue: 2 year: 2021 ident: 10.1016/j.clgc.2024.01.011_bib0011 article-title: Tumor frameshift mutation proportion predicts response to immunotherapy in mismatch repair-deficient prostate cancer publication-title: Oncologist doi: 10.1002/onco.13601 contributor: fullname: Sena – volume: 8 start-page: 1 issue: 2 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0013 article-title: Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA publication-title: J Immunother Cancer doi: 10.1136/jitc-2020-001065 contributor: fullname: Barata – ident: 10.1016/j.clgc.2024.01.011_bib0019 – volume: 15 start-page: 700 issue: 7 year: 2014 ident: 10.1016/j.clgc.2024.01.011_bib0003 article-title: Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial publication-title: Lancet Oncol doi: 10.1016/S1470-2045(14)70189-5 contributor: fullname: Kwon – volume: 37 start-page: 286 issue: 4 year: 2019 ident: 10.1016/j.clgc.2024.01.011_bib0008 article-title: Microsatellite instability is associated with the presence of lynch syndrome pan-cancer publication-title: J Clin Oncol doi: 10.1200/JCO.18.00283 contributor: fullname: Latham – volume: 161 start-page: 814 issue: 3 year: 2021 ident: 10.1016/j.clgc.2024.01.011_bib0015 article-title: Performance of next-generation sequencing for the detection of microsatellite instability in colorectal cancer with deficient DNA mismatch repair publication-title: Gastroenterology doi: 10.1053/j.gastro.2021.05.007 contributor: fullname: Ratovomanana – volume: 185 start-page: 563 issue: 3 year: 2022 ident: 10.1016/j.clgc.2024.01.011_bib0030 article-title: Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients publication-title: Cell doi: 10.1016/j.cell.2022.01.003 contributor: fullname: Nguyen – volume: 161 start-page: 1215 issue: 5 year: 2015 ident: 10.1016/j.clgc.2024.01.011_bib0006 article-title: Integrative clinical genomics of advanced prostate cancer publication-title: Cell doi: 10.1016/j.cell.2015.05.001 contributor: fullname: Robinson – volume: 34 start-page: 1402 issue: 12 year: 2016 ident: 10.1016/j.clgc.2024.01.011_bib0031 article-title: Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the prostate cancer clinical trials working group 3 publication-title: J Clin Oncol doi: 10.1200/JCO.2015.64.2702 contributor: fullname: Scher – volume: 75 start-page: 378 issue: 3 year: 2019 ident: 10.1016/j.clgc.2024.01.011_bib0012 article-title: Clinical features and therapeutic outcomes in men with advanced prostate cancer and DNA mismatch repair gene mutations publication-title: Eur Urol doi: 10.1016/j.eururo.2018.10.009 contributor: fullname: Antonarakis – volume: 578 start-page: 94 issue: 7793 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0026 article-title: The repertoire of mutational signatures in human cancer publication-title: Nature doi: 10.1038/s41586-020-1943-3 contributor: fullname: Alexandrov – volume: 23 start-page: 517 issue: 4 year: 2017 ident: 10.1016/j.clgc.2024.01.011_bib0024 article-title: HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures publication-title: Nat Med doi: 10.1038/nm.4292 contributor: fullname: Davies – volume: 38 start-page: 395 issue: 5 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0002 article-title: Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase II KEYNOTE-199 study publication-title: J Clin Oncol doi: 10.1200/JCO.19.01638 contributor: fullname: Antonarakis – volume: 38 start-page: 1 issue: 1 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0009 article-title: Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair–deficient cancer: results from the phase II KEYNOTE-158 study publication-title: J Clin Oncol doi: 10.1200/JCO.19.02105 contributor: fullname: Marabelle – volume: 39 start-page: 98 issue: 6 year: 2021 ident: 10.1016/j.clgc.2024.01.011_bib0034 article-title: Randomized phase II study evaluating the addition of pembrolizumab to radium-223 in metastatic castration-resistant prostate cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2021.39.6_suppl.98 contributor: fullname: Choudhury – volume: 141 start-page: 751 issue: 6 year: 2017 ident: 10.1016/j.clgc.2024.01.011_bib0029 article-title: Validation of OncoPanel: a targeted next-generation sequencing assay for the detection of somatic variants in cancer publication-title: Arch Pathol Lab Med doi: 10.5858/arpa.2016-0527-OA contributor: fullname: Garcia – volume: 91 start-page: 467 issue: 4 year: 1997 ident: 10.1016/j.clgc.2024.01.011_bib0037 article-title: Mutation in the mismatch repair gene Msh6 causes cancer susceptibility publication-title: Cell doi: 10.1016/S0092-8674(00)80433-X contributor: fullname: Edelmann – volume: 38 start-page: 489 issue: 4 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0005 article-title: Nivolumab plus ipilimumab for metastatic castration-resistant prostate cancer: preliminary analysis of patients in the CheckMate 650 trial publication-title: Cancer Cell doi: 10.1016/j.ccell.2020.08.007 contributor: fullname: Sharma – volume: 80 start-page: 1050 issue: 7 year: 2022 ident: 10.1016/j.clgc.2024.01.011_bib0018 article-title: Histopathological and genetic features of mismatch repair-deficient high-grade prostate cancer publication-title: Histopathology doi: 10.1111/his.14645 contributor: fullname: Wyvekens – volume: 5 start-page: 551 issue: 4 year: 2019 ident: 10.1016/j.clgc.2024.01.011_bib0016 article-title: Association of primary resistance to immune checkpoint inhibitors in metastatic colorectal cancer with misdiagnosis of microsatellite instability or mismatch repair deficiency status publication-title: JAMA Oncol doi: 10.1001/jamaoncol.2018.4942 contributor: fullname: Cohen – volume: 5 start-page: 1411 issue: 10 year: 2019 ident: 10.1016/j.clgc.2024.01.011_bib0001 article-title: Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab publication-title: JAMA Oncol doi: 10.1001/jamaoncol.2019.2187 contributor: fullname: Topalian – volume: 28 start-page: 1493 issue: 8 year: 2022 ident: 10.1016/j.clgc.2024.01.011_bib0022 article-title: Phase 1b clinical trial with alpelisib plus olaparib for patients with advanced triple-negative breast cancer publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-21-3045 contributor: fullname: Batalini – volume: 147 start-page: 2948 issue: 10 year: 2020 ident: 10.1016/j.clgc.2024.01.011_bib0036 article-title: Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors publication-title: Int J Cancer doi: 10.1002/ijc.33115 contributor: fullname: Salem |
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Snippet | Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to... INTRODUCTION/BACKGROUNDImmune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to... |
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SubjectTerms | Antibodies, Monoclonal, Humanized - therapeutic use Brain Neoplasms Colorectal Neoplasms Genomic signature Humans Immune checkpoint inhibitors Male Mismatch repair deficiency Neoplastic Syndromes, Hereditary - chemically induced Neoplastic Syndromes, Hereditary - drug therapy Pembrolizumab Prostatic Neoplasms, Castration-Resistant - drug therapy Prostatic Neoplasms, Castration-Resistant - genetics |
Title | A Panel-Based Mutational Signature of Mismatch Repair Deficiency is Associated With Durable Response to Pembrolizumab in Metastatic Castration-Resistant Prostate Cancer |
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