Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series
Background: Tumors with deficient mismatch repair (dMMR) have a favorable immunological phenotype permitting exploitation by immunotherapies. We aimed to assess our institutional experience of dMMR advanced gastrointestinal (GI) cancers treated with the PD-1 inhibitor pembrolizumab. Materials and Me...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Innovative Healthcare Institute
2018-07-01
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| Series: | Journal of Immunotherapy and Precision Oncology |
| Subjects: | |
| Online Access: | https://jipo.org/doi/pdf/10.4103/JIPO.JIPO_5_1 |
| _version_ | 1797962719014420480 |
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| author | David D Stenehjem Courtney C Cavalieri Eric Swanson Benjamin Solomon Jonathan Whisenant Dao Tran John Weis G Weldon Gilcrease Sunil Sharma Ignacio Garrido-Laguna |
| author_facet | David D Stenehjem Courtney C Cavalieri Eric Swanson Benjamin Solomon Jonathan Whisenant Dao Tran John Weis G Weldon Gilcrease Sunil Sharma Ignacio Garrido-Laguna |
| author_sort | David D Stenehjem |
| collection | DOAJ |
| description | Background: Tumors with deficient mismatch repair (dMMR) have a favorable immunological phenotype permitting exploitation by immunotherapies. We aimed to assess our institutional experience of dMMR advanced gastrointestinal (GI) cancers treated with the PD-1 inhibitor pembrolizumab. Materials and Methods: We conducted an observational cohort study of a clinical series of patients with dMMR metastatic GI cancers treated with pembrolizumab from 2015 to 2017. Patients were assessed for best response, time to and reason for discontinuation, and adverse events. Results: A total of 13 patients received at least one dose of pembrolizumab. Median age was 62 years (range 33–74 years). Diagnoses included colorectal (colorectal cancer [CRC], n = 7); extrahepatic and intrahepatic cholangiocarcinoma (EHCC, n = 2; n = 1); pancreatic (pancreatic ductal adenocarcinoma [PDAC], n = 2); and adenocarcinoma of the appendix (n = 1). Five patients received concurrent chemotherapy (FOLFOX or capecitabine) with pembrolizumab (200 mg intravenous [IV] q 2 weeks with FOLFOX or 2 mg/kg IV q 3 weeks with capecitabine). Pembrolizumab was administered 2 mg/kg IV q 3 weeks to all patients who received single-agent treatment. Eleven patients were evaluable for response assessment. Three patients had a complete response (CRC and two EHCC) and one of these patients received concomitant pembrolizumab and FOLFOX. Two patients had a partial response, one with PDAC (−88% per RECIST, continues on treatment after 15.7 months) and the other with CRC (−45% per RECIST, continues after 14.6 months), both patients received concomitant pembrolizumab and FOLFOX and are now maintained on single-agent pembrolizumab. The objective response rate was 42%. Three patients experienced immune-related adverse events requiring discontinuation. Conclusions: This single-institution case series confirms the activity of pembrolizumab in various GI cancers harboring dMMR. Future studies are warranted to determine the role of combinatorial treatment with chemotherapy and/or novel immunotherapies in this population. |
| first_indexed | 2024-04-11T01:17:17Z |
| format | Article |
| id | doaj.art-518196c78f6e47e7b0d8093b057286ec |
| institution | Directory Open Access Journal |
| issn | 2666-2345 2590-017X |
| language | English |
| last_indexed | 2024-04-11T01:17:17Z |
| publishDate | 2018-07-01 |
| publisher | Innovative Healthcare Institute |
| record_format | Article |
| series | Journal of Immunotherapy and Precision Oncology |
| spelling | doaj.art-518196c78f6e47e7b0d8093b057286ec2023-01-03T19:50:29ZengInnovative Healthcare InstituteJournal of Immunotherapy and Precision Oncology2666-23452590-017X2018-07-0116i2590-017X-1-1-1Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case SeriesDavid D Stenehjem0Courtney C Cavalieri1Eric Swanson2Benjamin Solomon3Jonathan Whisenant4Dao Tran5John Weis6G Weldon Gilcrease7Sunil Sharma8Ignacio Garrido-Laguna91 Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN3 Department of Pharmacy Services, Huntsman Cancer Institute at the University of Utah4 Department of Pathology, University of Utah5 Department of Internal Medicine, Division of Oncology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah5 Department of Internal Medicine, Division of Oncology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah1 Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota, Duluth, MN5 Department of Internal Medicine, Division of Oncology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah5 Department of Internal Medicine, Division of Oncology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah5 Department of Internal Medicine, Division of Oncology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah5 Department of Internal Medicine, Division of Oncology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UtahBackground: Tumors with deficient mismatch repair (dMMR) have a favorable immunological phenotype permitting exploitation by immunotherapies. We aimed to assess our institutional experience of dMMR advanced gastrointestinal (GI) cancers treated with the PD-1 inhibitor pembrolizumab. Materials and Methods: We conducted an observational cohort study of a clinical series of patients with dMMR metastatic GI cancers treated with pembrolizumab from 2015 to 2017. Patients were assessed for best response, time to and reason for discontinuation, and adverse events. Results: A total of 13 patients received at least one dose of pembrolizumab. Median age was 62 years (range 33–74 years). Diagnoses included colorectal (colorectal cancer [CRC], n = 7); extrahepatic and intrahepatic cholangiocarcinoma (EHCC, n = 2; n = 1); pancreatic (pancreatic ductal adenocarcinoma [PDAC], n = 2); and adenocarcinoma of the appendix (n = 1). Five patients received concurrent chemotherapy (FOLFOX or capecitabine) with pembrolizumab (200 mg intravenous [IV] q 2 weeks with FOLFOX or 2 mg/kg IV q 3 weeks with capecitabine). Pembrolizumab was administered 2 mg/kg IV q 3 weeks to all patients who received single-agent treatment. Eleven patients were evaluable for response assessment. Three patients had a complete response (CRC and two EHCC) and one of these patients received concomitant pembrolizumab and FOLFOX. Two patients had a partial response, one with PDAC (−88% per RECIST, continues on treatment after 15.7 months) and the other with CRC (−45% per RECIST, continues after 14.6 months), both patients received concomitant pembrolizumab and FOLFOX and are now maintained on single-agent pembrolizumab. The objective response rate was 42%. Three patients experienced immune-related adverse events requiring discontinuation. Conclusions: This single-institution case series confirms the activity of pembrolizumab in various GI cancers harboring dMMR. Future studies are warranted to determine the role of combinatorial treatment with chemotherapy and/or novel immunotherapies in this population.https://jipo.org/doi/pdf/10.4103/JIPO.JIPO_5_1case seriesdefective dna mismatch repairgastrointestinal malignanciesimmunotherapypembrolizumab |
| spellingShingle | David D Stenehjem Courtney C Cavalieri Eric Swanson Benjamin Solomon Jonathan Whisenant Dao Tran John Weis G Weldon Gilcrease Sunil Sharma Ignacio Garrido-Laguna Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series Journal of Immunotherapy and Precision Oncology case series defective dna mismatch repair gastrointestinal malignancies immunotherapy pembrolizumab |
| title | Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series |
| title_full | Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series |
| title_fullStr | Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series |
| title_full_unstemmed | Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series |
| title_short | Pembrolizumab in Advanced Gastrointestinal Malignancies with Defective DNA Mismatch Repair: A Case Series |
| title_sort | pembrolizumab in advanced gastrointestinal malignancies with defective dna mismatch repair a case series |
| topic | case series defective dna mismatch repair gastrointestinal malignancies immunotherapy pembrolizumab |
| url | https://jipo.org/doi/pdf/10.4103/JIPO.JIPO_5_1 |
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