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Immune checkpoint inhibitors for patients with isolated peritoneal carcinomatosis from dMMR/MSI-H colorectal cancer, a BIG-RENAPE collaboration

  • Solenn Barraud
    Affiliations
    Sorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP, and INSERM UMRS 938, Équipe Instabilité des Microsatellites et Cancer, Équipe Labellisée par la Ligue Nationale Contre le Cancer et SIRIC CURAMUS, Centre de recherche Saint Antoine, Paris, France
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  • David Tougeron
    Affiliations
    Université de Poitiers, Faculté de Médecine et de Pharmacie and Department of Hepatology and Gastroenterology, Centre hospitalo-universitaire de Poitiers, Poitiers, France
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  • Laurent Villeneuve
    Affiliations
    Clinical Research and Epidemiological Unit, Department of Public Health, Lyon University Hospital, EA 3738, University of Lyon, Lyon, France
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  • Clarisse Eveno
    Affiliations
    Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, and UMR- S1277- CANTHER Laboratory, "Cancer Heterogeneity, Plasticity and Resistance to Therapies", Lille, France
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  • Arnaud Bayle
    Affiliations
    Drug Development Department (DITEP), Gustave Roussy, Villejuif, France; Oncostat U1018, Inserm, Université Paris-Saclay, Équipe Labellisée Ligue Contre le Cancer, Villejuif, France
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  • Yann Parc
    Affiliations
    Sorbonne Université, Department of Digestive Surgery, Hôpital Saint-Antoine, AP-HP, and INSERM UMRS 938, Équipe Instabilité des Microsatellites et Cancer, Équipe Labellisée par la Ligue Nationale Contre le Cancer et SIRIC CURAMUS, Centre de recherche Saint Antoine, Paris, France
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  • Marc Pocard
    Affiliations
    Hepato-Biliary-Pancreatic Gastrointestinal Surgery and Liver Transplantation, Pitié-Salpêtrière Hospital, Assistance Publique/Hôpitaux de Paris, and Université Paris Cité, UMR INSERM 1275 CAP Paris-Tech, Lariboisière Hospital, F-75010 Paris, France
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  • Thierry André
    Affiliations
    Sorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP, and INSERM UMRS 938, Équipe Instabilité des Microsatellites et Cancer, Équipe Labellisée par la Ligue Nationale Contre le Cancer et SIRIC CURAMUS, Centre de recherche Saint Antoine, Paris, France
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  • Romain Cohen
    Correspondence
    Corresponding author at: Hôpital Saint-Antoine, 184 rue du faubourg Saint-Antoine, 75012 Paris, France.
    Affiliations
    Sorbonne Université, Department of Medical Oncology, Hôpital Saint-Antoine, AP-HP, and INSERM UMRS 938, Équipe Instabilité des Microsatellites et Cancer, Équipe Labellisée par la Ligue Nationale Contre le Cancer et SIRIC CURAMUS, Centre de recherche Saint Antoine, Paris, France
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Published:October 18, 2022DOI:https://doi.org/10.1016/j.dld.2022.09.015

      Abstract

      Background

      Immunotherapy with immune checkpoint inhibitors has significantly improved the survival of patients with MSI/dMMR mCRC. These tumors are associated with a specific metastatic spread, i.e. frequent peritoneal carcinomatosis (PC) that may be treated surgically when there is no other metastatic location. We aimed at evaluating the prognosis of patients treated with immune checkpoint inhibitors for MSI/dMMR mCRC with isolated PC.

      Material and Methods

      All consecutive patients with isolated PC from MSI/dMMR mCRC, initially considered as unresectable by multidisciplinary team meeting, treated with immune checkpoint inhibitors were included in this French multicenter cohort study.

      Results

      Among 45 patients included, we observed 11 complete responses and 10 partial responses for an overall response rate iRECIST of 46%. After a median follow-up of 24.4 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. Seven of the eight patients who underwent cytoreductive surgery after treatment with anti-PD1 ± anti-CTLA-4 were in complete pathologic response.

      Conclusion

      These results demonstrate long-term benefit of immune checkpoint inhibitors for patients with isolated PC from MSI/dMMR mCRC. Such treatment appears as the best therapeutic option for patients with isolated PC from MSI/dMMR mCRC. With a majority of pathological complete responses for patients who underwent surgery for residual lesions, the value of such therapeutic strategy remains unknown.

      Keywords

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      References

        • Quere P.
        • Facy O.
        • Manfredi S.
        • Jooste V.
        • Faivre J.
        • Lepage C.
        • et al.
        Epidemiology, management, and survival of peritoneal carcinomatosis from colorectal cancer: a population-based study.
        Dis Colon Rectum. 2015; 58: 743‑52
        • Segelman J.
        • Granath F.
        • Holm T.
        • Machado M.
        • Mahteme H.
        • Martling A.
        Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer.
        Br. J. Surg. 2012; 99: 699‑705
        • Jayne D.G.
        • Fook S.
        • Loi C.
        • Seow-Choen F.
        Peritoneal carcinomatosis from colorectal cancer.
        Br. J. Surg. 2002; 89: 1545‑50
        • Franko J.
        • Shi Q.
        • Meyers J.P.
        • Maughan T.S.
        • Adams R.A.
        • Seymour M.T.
        • et al.
        Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database.
        Lancet Oncol. 2016; 17: 1709‑19
        • Quénet F.
        • Elias D.
        • Roca L.
        • Goéré D.
        • Ghouti L.
        • Pocard M.
        • et al.
        Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.
        Lancet Oncol. 2021; 22: 256‑66
        • Venderbosch S.
        • Nagtegaal I.D.
        • Maughan T.S.
        • Smith C.G.
        • Cheadle J.P.
        • Fisher D.
        • et al.
        Mismatch repair status and braf mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS Studies.
        Clin. Cancer Res. 2014; 20: 5322‑30
        • Randrian V.
        • Evrard C.
        • Tougeron D.
        Microsatellite Instability in Colorectal Cancers: carcinogenesis, Neo-Antigens, Immuno-Resistance and Emerging Therapies.
        Cancers (Basel). 2021; 13: 3063
        • Marisa L.
        • Svrcek M.
        • Collura A.
        • Becht E.
        • Cervera P.
        • Wanherdrick K.
        • et al.
        The balance between cytotoxic t-cell lymphocytes and immune checkpoint expression in the prognosis of colon tumors.
        J. Natl. Cancer Inst. 2018; 110
        • André T.
        • Shiu K.K.
        • Kim T.W.
        • Jensen B.V.
        • Jensen L.H.
        • Punt C.
        • et al.
        Pembrolizumab in microsatellite-instability-high advanced colorectal cancer.
        N. Engl. J. Med. 2020; 383: 2207‑18
        • Andre T.
        • Shiu K.K.
        • Kim T.W.
        • Jensen B.V.
        • Jensen L.H.
        • Punt C.J.A.
        • et al.
        Final overall survival for the phase III KN177 study: pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).
        J. Clin. Oncol. 2021; 39: 3500‑3500
        • Le D.T.
        • Uram J.N.
        • Wang H.
        • Bartlett B.R.
        • Kemberling H.
        • Eyring A.D.
        • et al.
        PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.
        N Engl J Med. 2015; 372: 2509‑20
        • Overman M.J.
        • McDermott R.
        • Leach J.L.
        • Lonardi S.
        • Lenz H.J.
        • Morse M.A.
        • et al.
        Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study.
        Lancet Oncol. 2017; 18: 1182‑91
        • Diaz L.A.
        • Shiu K.K.
        • Kim T.W.
        • Jensen B.V.
        • Jensen L.H.
        • Punt C.
        • et al.
        Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study.
        Lancet Oncol. 2022; 23: 659‑70
        • Tran B.
        • Kopetz S.
        • Tie J.
        • Gibbs P.
        • Jiang Z.Q.
        • Lieu C.H.
        • et al.
        Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer.
        Cancer. 2011; 117: 4623‑32
        • Tougeron D.
        • Sueur B.
        • Zaanan A.
        • de la Fouchardiére C.
        • Sefrioui D.
        • Lecomte T.
        • et al.
        Prognosis and chemosensitivity of deficient MMR phenotype in patients with metastatic colorectal cancer: an AGEO retrospective multicenter study.
        Int. J. Cancer. 2020; 147: 285‑96
        • Sugarbaker P.H.
        Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis.
        Semin Surg Oncol. 1998; 14: 254‑61
        • Loupakis F.
        • Depetris I.
        • Biason P.
        • Intini R.
        • Prete A.A.
        • Leone F.
        • et al.
        Prediction of benefit from checkpoint inhibitors in mismatch repair deficient metastatic colorectal cancer: role of tumor infiltrating lymphocytes.
        Oncologist. 2020; 25: 481‑7
        • Mandal R.
        • Samstein R.M.
        • Lee K.W.
        • Havel J.J.
        • Wang H.
        • Krishna C.
        • et al.
        Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response.
        Science. 2019; 364: 485‑91
        • Schrock A.B.
        • Ouyang C.
        • Sandhu J.
        • Sokol E.
        • Jin D.
        • Ross J.S.
        • et al.
        Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer.
        Ann. Oncol. Off. J. Eur. Soc. Med. Oncol. 2019; 30: 1096‑103
        • Tominaga T.
        • Nonaka T.
        • Fukuda A.
        • Moriyama M.
        • Oyama S.
        • Ishii M.
        • et al.
        Pathological complete response to pembrolizumab in patients with metastatic ascending colon cancer with microsatellite instability.
        Clin. J. Gastroenterol. 2021;
        • Ludford K.
        • Cohen R.
        • Svrcek M.
        • Foo W.C.
        • Colle R.
        • Parc Y.
        • et al.
        Pathological tumor response following immune checkpoint blockade for deficient mismatch repair advanced colorectal cancer.
        J. Nat.l Cancer Inst. 2021; 113: 208‑11
        • Keating M.
        • Giscombe L.
        • Tannous T.
        • Hartshorn K.
        Prolonged treatment response to pembrolizumab in a patient with pretreated metastatic colon cancer and lynch syndrome.
        Case Rep. Oncol. Med. 2019; 20193847672
        • Fucà G.
        • Cohen R.
        • Lonardi S.
        • Shitara K.
        • Elez M.E.
        • Fakih M.
        • et al.
        Ascites and resistance to immune checkpoint inhibition in dMMR/MSI-H metastatic colorectal and gastric cancers.
        J. Immunother. Cancer. 2022; 10e004001