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Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study

Author

Listed:
  • Anneke L. Eerkens

    (University Medical Centre Groningen)

  • Koen Brummel

    (University Medical Centre Groningen)

  • Annegé Vledder

    (University Medical Centre Groningen)

  • Sterre T. Paijens

    (Erasmus University Medical Centre)

  • Marta Requesens

    (University Medical Centre Groningen)

  • Dominik Loiero

    (University of Zurich)

  • Nienke Rooij

    (University Medical Centre Groningen)

  • Annechien Plat

    (University Medical Centre Groningen)

  • Floris-Jan Haan

    (University Medical Centre Groningen)

  • Patty Klok

    (University Medical Centre Groningen)

  • Refika Yigit

    (University Medical Centre Groningen)

  • Thijs Roelofsen

    (University Medical Centre Groningen)

  • Natascha M. Lange

    (Isala)

  • Rie Klomp

    (Treant)

  • David Church

    (University of Oxford
    John Radcliffe Hospital)

  • Arja Elst

    (University Medical Centre Groningen)

  • René Wardenaar

    (University Medical Centre Groningen)

  • Diana Spierings

    (University Medical Centre Groningen)

  • Floris Foijer

    (University Medical Centre Groningen)

  • Viktor Hendrik Koelzer

    (University of Zurich)

  • Tjalling Bosse

    (Leiden University Medical Centre)

  • Joost Bart

    (University Medical Centre Groningen)

  • Mathilde Jalving

    (University Medical Centre Groningen)

  • Anna K. L. Reyners

    (University Medical Centre Groningen)

  • Marco Bruyn

    (University Medical Centre Groningen)

  • Hans W. Nijman

    (University Medical Centre Groningen)

Abstract

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.

Suggested Citation

  • Anneke L. Eerkens & Koen Brummel & Annegé Vledder & Sterre T. Paijens & Marta Requesens & Dominik Loiero & Nienke Rooij & Annechien Plat & Floris-Jan Haan & Patty Klok & Refika Yigit & Thijs Roelofsen, 2024. "Neoadjuvant immune checkpoint blockade in women with mismatch repair deficient endometrial cancer: a phase I study," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52098-8
    DOI: 10.1038/s41467-024-52098-8
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