Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study

E Alouani; M Mercier; C Flecchia; E Auclin; A Hollebecque; T Mazard; A Turpin; S Pernot; R Cohen; M Dutherage; S Kim; F Sclafani; M Ben-Abdelghani; C Herve; T Aparicio; C De La Fouchardière; G Perkins; V Hautefeuille; M Jaffrelot; C Gallois; V Bongard; D Tougeron; J Taïeb; R Guimbaud

doi:10.1016/j.esmoop.2023.101574

Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study

ESMO Open. 2023 Jun;8(3):101574. doi: 10.1016/j.esmoop.2023.101574. Epub 2023 May 25.

Authors

E Alouani¹, M Mercier², C Flecchia³, E Auclin⁴, A Hollebecque⁵, T Mazard⁶, A Turpin⁷, S Pernot⁸, R Cohen⁹, M Dutherage¹⁰, S Kim¹¹, F Sclafani¹², M Ben-Abdelghani¹³, C Herve¹⁴, T Aparicio¹⁵, C De La Fouchardière¹⁶, G Perkins¹⁷, V Hautefeuille¹⁸, M Jaffrelot¹⁹, C Gallois³, V Bongard²⁰, D Tougeron², J Taïeb³, R Guimbaud¹⁹

Affiliations

¹ Digestive Oncology Department, Rangueil Hospital, University Hospital of Toulouse, Toulouse. Electronic address: alouani.e@chu-toulouse.fr.
² University of Poitiers and Gastroenterology and Hepatology Department, Poitiers University Hospital, Poitiers.
³ Institut du Cancer Paris CARPEM, Université Paris Cité, Hôpital Européen Georges Pompidou, Assistance Publique - Hôpitaux de Paris, Paris.
⁴ Department of Oncology, Hôpital Européen Georges Pompidou, AP-HP Centre, Université Paris Cité, Paris.
⁵ Drug Development Department (DITEP), Gustave Roussy, Saclay University of Paris, Villejuif.
⁶ Institute de Recherche en Cancérologie de Montpellier, INSERM, University of Montpellier, ICM, Montpellier.
⁷ Department of Medical Oncology, CNRS UMR9020, Inserm UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University Lille, CHU Lille, Lille.
⁸ Department of Digestive Oncology, Institut Bergonié, Bordeaux.
⁹ Sorbonne University, Department of Medical Oncology, Saint-Antoine Hospital, AP-HP, SIRIC CURAMUS, INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Paris.
¹⁰ Department of Medical Oncology, Henri Becquerel Centre, Rouen.
¹¹ Department of Medical Oncology, University Hospital of Besançon, Besançon, France.
¹² Department of Digestive Oncology, The Brussels University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
¹³ Medical Oncology Department, ICANS, Strasbourg.
¹⁴ Clinique Mutualiste de Grenoble, Institut de cancérologie Daniel Hollard, Grenoble.
¹⁵ Gastroenterology Department, Saint Louis Hospital, Paris.
¹⁶ Medical Oncology Department, Leon Berard Center, Lyon.
¹⁷ Department of Gastroenterology, University Hospital Pontchaillou, Rennes.
¹⁸ Department of Hepato-Gastroenterology and Digestive Oncology, CHU Amiens Picardie, Amiens.
¹⁹ Digestive Oncology Department, Rangueil Hospital, University Hospital of Toulouse, Toulouse.
²⁰ Epidemiology Department CHU de Toulouse, UMR 1295, Centre d'Epidémiologie et de Recherche en santé des Populations, Université Paul Sabatier Toulouse III-Inserm, Toulouse, France.

Abstract

Background: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce.

Patients and methods: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded.

Results: Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009).

Conclusions: Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

Keywords: immune checkpoint inhibitors (ICI); immunotherapy; metastatic colorectal cancer (mCRC); microsatellite instability (MSI); mismatch repair deficient (MMRd).

Publication types

Multicenter Study

MeSH terms

Colonic Neoplasms*
Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / therapy
DNA Mismatch Repair
Humans
Immunotherapy
Peritoneal Neoplasms*
Retrospective Studies

Supplementary concepts

Turcot syndrome