Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial
Background In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)—mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).Methods A multicenter phase two study was performed in wo...
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BMJ Publishing Group
2021-06-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/6/e002255.full |
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| author | Linda Mileshkin Elizabeth Barnes Tarek Meniawy Kristy Robledo Michael Friedlander Geraldine Goss Jermaine Coward Yoland Antill Michelle Cummins Sally Baron-Hay Martin R Stockler Catherine Shannon Philip Beale Peey-Sei Kok Deborah Smith Sonia Yip Amanda Spurdle Yeh Chen Lee Janine Lombard John Andrews |
| author_facet | Linda Mileshkin Elizabeth Barnes Tarek Meniawy Kristy Robledo Michael Friedlander Geraldine Goss Jermaine Coward Yoland Antill Michelle Cummins Sally Baron-Hay Martin R Stockler Catherine Shannon Philip Beale Peey-Sei Kok Deborah Smith Sonia Yip Amanda Spurdle Yeh Chen Lee Janine Lombard John Andrews |
| author_sort | Linda Mileshkin |
| collection | DOAJ |
| description | Background In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)—mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).Methods A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics.Results Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1–2.Conclusion Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR.Trial registration numbers ANZGOG1601, ACTRN12617000106336, and NCT03015129. |
| format | Article |
| id | doaj-art-d96d05924ab04b6c8cd23204887b78f3 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d96d05924ab04b6c8cd23204887b78f32025-08-20T02:13:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-06-019610.1136/jitc-2020-002255Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trialLinda Mileshkin0Elizabeth Barnes1Tarek Meniawy2Kristy Robledo3Michael Friedlander4Geraldine Goss5Jermaine Coward6Yoland Antill7Michelle Cummins8Sally Baron-Hay9Martin R Stockler10Catherine Shannon11Philip Beale12Peey-Sei Kok13Deborah Smith14Sonia Yip15Amanda Spurdle16Yeh Chen Lee17Janine Lombard18John Andrews19Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, AustraliaNHMRC Clinical Trial Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, AustraliaLinear Clinical Research and the University of Western Australia, Nedlands, Western Australia, AustraliaBiostatistics and Research Methodology, University of Sydney NHMRC Clinical Trials Centre, Sydney, New South Wales, Australia4Prince of Wales and Royal Hospital for Women, Department of Medical Oncology, Sydney, AustraliaMedical Oncology, Monash Medical Centre Clayton, Clayton, Victoria, AustraliaFaculty of Medicine and ICON Cancer Care Centre, The University of Queensland, Brisbane, Queensland, AustraliaMedical Oncology, Cabrini Health, Malvern, Victoria, AustraliaNHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, AustraliaMedical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, AustraliaUniversity of Sydney, NHMRC Clinical Trials Centre, Camperdown, New South Wales, AustraliaMater Cancer Care Centre, Mater Hospital, South Brisbane, Queensland, AustraliaDepartment of Medical Oncology, Concord Hospital, Concord, New South Wales, AustraliaNHMRC Clinical Trials Centre, University of Sydney, Camperdown, New South Wales, AustraliaMater Pathology, Mater Research and University of Queensland, Brisbane, Queensland, AustraliaNHMRC Clinical Trials Centre, Camperdown, New South Wales, AustraliaMolecular Cancer Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, AustraliaUniversity of New South Wales Prince of Wales Clinical School, Randwick, New South Wales, AustraliaMedical Oncology, Calvary Mater Newcastle, Hunter Region Mail Centre, New South Wales, AustraliaUniversity of Sydney, NHMRC Clinical Trials Centre, Camperdown, New South Wales, AustraliaBackground In this study, we assessed the activity of durvalumab, an antibody to programmed death ligand-1, in two cohorts of women with advanced endometrial cancers (AEC)—mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR).Methods A multicenter phase two study was performed in women with AEC with pMMR tumor progressing after one to three lines of chemotherapy and women with AEC with dMMR tumor progressing after zero to three lines of chemotherapy. Mismatch repair status was based on immunohistochemistry expression. All women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. The primary endpoint was objective tumor response by RECIST V.1.1 modified for immune-based therapeutics.Results Seventy-one women were recruited: 35 dMMR and 36 pMMR. Median follow-up was 19 vs 21 months in dMMR versus pMMR, respectively. Median age was 67 years. Histology in dMMR versus pMMR included endometrioid (94% vs 57%) and serous (0% vs 31%) and was high grade in 26% vs 74%. The objective tumor response rate (OTRR) in the dMMR cohort was 47% (17/36, 95% CI 32 to 63), including 6 complete responses and 11 partial responses (PRs)) vs 3% in the pMMR cohort (1/35, 95% CI 1 to 15, PR). In the dMMR cohort, durvalumab was the first-line therapy in 58% (OTRR 57%) and the second-line therapy in 39% (OTRR 38%). Median progression-free survival was 8.3 months in the dMMR cohort vs 1.8 months in the pMMR cohort. The 12-month overall survival (OS) rate was 71% in dMMR vs 51% in pMMR, with median OS not reached for dMMR vs 12 months for pMMR. Immune-related adverse events occurred in 14 women, mostly grades 1–2.Conclusion Durvalumab monotherapy showed promising activity and acceptable safety in AEC with dMMR regardless of prior lines of chemotherapy, but activity was limited in AEC with pMMR.Trial registration numbers ANZGOG1601, ACTRN12617000106336, and NCT03015129.https://jitc.bmj.com/content/9/6/e002255.full |
| spellingShingle | Linda Mileshkin Elizabeth Barnes Tarek Meniawy Kristy Robledo Michael Friedlander Geraldine Goss Jermaine Coward Yoland Antill Michelle Cummins Sally Baron-Hay Martin R Stockler Catherine Shannon Philip Beale Peey-Sei Kok Deborah Smith Sonia Yip Amanda Spurdle Yeh Chen Lee Janine Lombard John Andrews Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial Journal for ImmunoTherapy of Cancer |
| title | Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial |
| title_full | Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial |
| title_fullStr | Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial |
| title_full_unstemmed | Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial |
| title_short | Clinical activity of durvalumab for patients with advanced mismatch repair-deficient and repair-proficient endometrial cancer. A nonrandomized phase 2 clinical trial |
| title_sort | clinical activity of durvalumab for patients with advanced mismatch repair deficient and repair proficient endometrial cancer a nonrandomized phase 2 clinical trial |
| url | https://jitc.bmj.com/content/9/6/e002255.full |
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