Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study
Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2024
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| _version_ | 1811141301535506432 |
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| author | Eerkens, AL Brummel, K Vledder, A Paijens, ST Requesens, M Loiero, D van Rooij, N Plat, A Haan, F Klok, P Yigit, R Roelofsen, T de Lange, NM Klomp, R Church, D ter Elst, A Wardenaar, R Spierings, D Foijer, F Koelzer, VH Bosse, T Bart, J Jalving, M Reyners, AKL |
| author_facet | Eerkens, AL Brummel, K Vledder, A Paijens, ST Requesens, M Loiero, D van Rooij, N Plat, A Haan, F Klok, P Yigit, R Roelofsen, T de Lange, NM Klomp, R Church, D ter Elst, A Wardenaar, R Spierings, D Foijer, F Koelzer, VH Bosse, T Bart, J Jalving, M Reyners, AKL |
| author_sort | Eerkens, AL |
| collection | OXFORD |
| description | Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment. |
| first_indexed | 2024-09-25T04:35:42Z |
| format | Journal article |
| id | oxford-uuid:d7e1350c-19f1-4d20-b6e3-e91c04a4ebe5 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:35:42Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:d7e1350c-19f1-4d20-b6e3-e91c04a4ebe52024-09-12T20:03:55ZNeoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d7e1350c-19f1-4d20-b6e3-e91c04a4ebe5EnglishJisc Publications RouterNature Research2024Eerkens, ALBrummel, KVledder, APaijens, STRequesens, MLoiero, Dvan Rooij, NPlat, AHaan, FKlok, PYigit, RRoelofsen, Tde Lange, NMKlomp, RChurch, Dter Elst, AWardenaar, RSpierings, DFoijer, FKoelzer, VHBosse, TBart, JJalving, MReyners, AKLNeoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment. |
| spellingShingle | Eerkens, AL Brummel, K Vledder, A Paijens, ST Requesens, M Loiero, D van Rooij, N Plat, A Haan, F Klok, P Yigit, R Roelofsen, T de Lange, NM Klomp, R Church, D ter Elst, A Wardenaar, R Spierings, D Foijer, F Koelzer, VH Bosse, T Bart, J Jalving, M Reyners, AKL Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study |
| title | Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study |
| title_full | Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study |
| title_fullStr | Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study |
| title_full_unstemmed | Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study |
| title_short | Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study |
| title_sort | neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer a phase i study |
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