Efficacy of Perioperative Pembrolizumab in Mismatch Repair Deficient/Microsatellite Unstable Localized Colorectal Cancers: Results of the Phase II Trial IMHOTEP
PURPOSE: Mismatch repair deficiency (dMMR) or microsatellite instability (MSI) represents a distinct phenotype among solid tumors resulting in the generation of highly immunogenic neoantigens. Pembrolizumab has been approved in first-line unresectable or metastatic dMMR/MSI colorectal cancers (CRC). We aimed to assess efficacy and tolerance of perioperative pembrolizumab in dMMR/MSI CRC. PATIENTS AND METHODS: The prospective multicenter phase II trial IMHOTEP enrolled patients with localized resectable dMMR/MSI CRC to receive one or two cycles of IV pembrolizumab 400 mg once every 6 weeks before surgery and 1-year total duration thereafter. The primary end point was pathologic complete response (pCR) rate (ypT0N0). Secondary objectives included safety, event-free survival, and overall survival. RESULTS: = .0125). With a median follow-up of 24.5 (95% CI, 23.3 to 25.6) months, three disease recurrences occurred. Grade ≥3 immune-related toxicities were reported in 14 (15.7%) patients including one grade 5 (myasthenia). CONCLUSION: The IMHOTEP trial showed promising results, with pCR achieved after one or two cycles of neoadjuvant pembrolizumab in 53% of patients with dMMR/MSI CRC. To our knowledge, this prospective study is the first to demonstrate the feasibility and the safety of perioperative pembrolizumab.
Authors
- Méher Ben Abdelghani (ORCID: https://orcid.org/0000-0002-9105-6346)
- Philippe Rochigneux (ORCID: https://orcid.org/0000-0001-7932-0530)
- Marine Jary (ORCID: https://orcid.org/0000-0001-7502-7708)
- David Pérol (ORCID: https://orcid.org/0000-0002-6429-7419)
- Emmanuelle Samalin-Scalzi
- Ellen Blanc
- Aziz Zaanan (ORCID: https://orcid.org/0000-0001-8372-5653)
- David Tougeron (ORCID: https://orcid.org/0000-0002-8065-9635)
- Ludovic Evesque (ORCID: https://orcid.org/0000-0001-9537-6454)
- Aymeric de Montfort
- Vincent Hautefeuille (ORCID: https://orcid.org/0000-0003-2735-6448)
- Émilie Soularue (ORCID: https://orcid.org/0000-0003-3223-5720)
- Clélia Coutzac (ORCID: https://orcid.org/0000-0002-8347-6957)
- Christelle de la Fouchardière (ORCID: https://orcid.org/0000-0003-2291-5693)
- Nicolas Williet (ORCID: https://orcid.org/0000-0002-7296-5464)
- Olivier Dubreuil (ORCID: https://orcid.org/0000-0003-0525-0423)
- Samuel Le Sourd
- R Cohen
- Guillaume Piessen (ORCID: https://orcid.org/0000-0001-8243-8310)
- Frederic Bibeau
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Montpellier (FR)
- Aix-Marseille Université (FR)
- Université de Lille (FR)
- Sorbonne Université (FR)
- Centre Hospitalier Universitaire de Besançon (FR)
- Institute Mutualiste Montsouris (FR)
- La Ligue Contre le Cancer (FR)
- Centre Hospitalier Universitaire Amiens-Picardie (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Européen Georges-Pompidou (FR)
- Hôpital Saint-Antoine (FR)
- Centre Léon Bérard (FR)
- Hôpital Européen (FR)
- Centre Eugène Marquis (FR)
- Centre Hospitalier Universitaire de Poitiers (FR)
- Groupe Hospitalier Diaconesses Croix Saint-Simon (FR)
- Centre de Recherche en Cancérologie de Lyon (FR)
- Centre Hospitalier Universitaire de Clermont-Ferrand (FR)
- Centre de Recherche Saint-Antoine (FR)
- Institut de Recherche en Cancérologie de Montpellier (FR)
- Institut Paoli-Calmettes (FR)
- Centre Antoine Lacassagne (FR)
- Centre Hospitalier Universitaire de Saint-Étienne (FR)
Publication Details
- Journal
- Journal of Clinical Oncology
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1200/jco-25-02169
- Primary Topic
- Genetic factors in colorectal cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00