Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA
To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patie...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001065.full |
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| _version_ | 1849221763301376000 |
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| author | Neeraj Agarwal Oliver Sartor Brian Lewis Hani Babiker Elisa Ledet Lesli Kiedrowski Pedro Barata Roberto Nussenzveig Benjamin Gerendash Ellen Jaeger Whitley Hatton Jodi Layton Alan Bryce Cy Stein Philip Saylor |
| author_facet | Neeraj Agarwal Oliver Sartor Brian Lewis Hani Babiker Elisa Ledet Lesli Kiedrowski Pedro Barata Roberto Nussenzveig Benjamin Gerendash Ellen Jaeger Whitley Hatton Jodi Layton Alan Bryce Cy Stein Philip Saylor |
| author_sort | Neeraj Agarwal |
| collection | DOAJ |
| description | To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3–12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4–7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H. |
| format | Article |
| id | doaj-art-e6bd68468cf64ae9a5dc5488cc01cd89 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e6bd68468cf64ae9a5dc5488cc01cd892024-11-10T19:10:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001065Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNANeeraj Agarwal0Oliver Sartor1Brian Lewis2Hani Babiker3Elisa Ledet4Lesli Kiedrowski5Pedro Barata6Roberto Nussenzveig7Benjamin Gerendash8Ellen Jaeger9Whitley Hatton10Jodi Layton11Alan Bryce12Cy Stein13Philip Saylor145University of Utah, Salt Lake City, UT, USAAff13 grid.265219.b0000000122178588Tulane University School of Medicine 1430 Tulane Ave, SL-42 70112 New Orleans LA USAretired secondary teacherUniversity of Arizona Cancer Center, Tucson, Arizona, USA1 Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA1Guardant Health, Inc., Redwood City, CA, USA1 Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA2 Department of Medical Oncology, University of Utah, Salt Lake City, Utah, USA3 Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA1 Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA1 Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA1 Deming Department of Medicine, Tulane University, New Orleans, Louisiana, USA5 Department of Oncology, Mayo Clinic, Scottsdale, Arizona, USA3 Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, USA9 Department of Oncology, Massachusetts General Hospital, Boston, Massachusetts, USATo report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3–12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4–7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.https://jitc.bmj.com/content/8/2/e001065.full |
| spellingShingle | Neeraj Agarwal Oliver Sartor Brian Lewis Hani Babiker Elisa Ledet Lesli Kiedrowski Pedro Barata Roberto Nussenzveig Benjamin Gerendash Ellen Jaeger Whitley Hatton Jodi Layton Alan Bryce Cy Stein Philip Saylor Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA Journal for ImmunoTherapy of Cancer |
| title | Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA |
| title_full | Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA |
| title_fullStr | Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA |
| title_full_unstemmed | Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA |
| title_short | Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA |
| title_sort | clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high msi h detected by circulating tumor dna |
| url | https://jitc.bmj.com/content/8/2/e001065.full |
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