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Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer

  • 0From Sorbonne Université, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Paris (T.A.), Hopital Foch, Suresnes (J.B.), and Institut Paoli-Calmettes (C.F.), and La Timone, Aix Marseille Université (L.D.), Marseille - all in France; Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona (E.E.), Hospital Universitario Virgen del Rocío, Seville (M.L.L.), Institut Català d'Oncologia, Hospital Universitario Germans Trias i Pujol, Badalona (J.L.M.M.), and Hospital Universitario 12 de Octubre, Imas12, Medicine Department-UCM, Madrid (R.G.-C.) - all in Spain; University Hospitals Gasthuisberg and University of Leuven (KU Leuven), Leuven, Belgium (E.V.C.); the University Hospital of Southern Denmark, Vejle Hospital, Vejle (L.H.J.); Hospital Universitario Fundacion Favaloro, Buenos Aires (G.M.); Centrul de Oncologie Sf Nectarie, Craiova, Romania (M.S.); the National Cancer Center Hospital East, Chiba, Japan (T.Y.); Shanghai East Hospital, Shanghai, China (J.L.); the University of Southern California Norris Comprehensive Cancer Center, Los Angeles (H.-J.L.); Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome (G.T.), and Veneto Institute of Oncology IOV-IRCCS, Padua (S.L.) - both in Italy; the Netherlands Cancer Institute, Amsterdam (M.C.); Cancer Research SA, Adelaide, SA, Australia (R.J.); Hematology-Oncology Practice Eppendorf (HOPE) and University Cancer Center Hamburg (UCCH), Hamburg, Germany (E.G.); the Institute of Cancer of São Paulo, São Paulo (M.I.B.); Adana City Education and Research Hospital, Adana, Turkey (T. Cil); and Bristol Myers Squibb, Princeton, NJ (E.C., T. Chen, M.L., M.D., S.A.).
The New England Journal of Medicine +

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November 27, 2024

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November 27, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Nivolumab plus ipilimumab significantly improved progression-free survival in patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer compared to chemotherapy. This immunotherapy combination offers a superior first-line treatment option for this patient population.

Area Of Science

  • Oncology
  • Immunotherapy
  • Gastrointestinal Cancers

Background

  • Metastatic colorectal cancer (mCRC) with MSI-H or dMMR status historically shows poor response to standard chemotherapy.
  • Nivolumab plus ipilimumab has demonstrated potential clinical benefits in prior non-randomized studies for MSI-H/dMMR mCRC.

Purpose Of The Study

  • To evaluate the efficacy of nivolumab plus ipilimumab compared to chemotherapy as a first-line treatment for unresectable or metastatic colorectal cancer with MSI-H or dMMR status.

Main Methods

  • Phase 3, open-label trial randomizing patients with MSI-H/dMMR mCRC to nivolumab plus ipilimumab, nivolumab alone, or chemotherapy (2:2:1 ratio).
  • Primary endpoints focused on progression-free survival (PFS) comparing nivolumab plus ipilimumab versus chemotherapy in first-line treatment.
  • Interim analysis assessed the primary endpoint of PFS for nivolumab plus ipilimumab versus chemotherapy.

Main Results

  • In 255 patients with centrally confirmed MSI-H/dMMR tumors, nivolumab plus ipilimumab showed significantly better PFS than chemotherapy (P<0.001).
  • 24-month PFS was 72% for nivolumab plus ipilimumab versus 14% for chemotherapy.
  • Grade 3/4 adverse events were lower with nivolumab plus ipilimumab (23%) compared to chemotherapy (48%).

Conclusions

  • Nivolumab plus ipilimumab demonstrates superior progression-free survival compared to chemotherapy for first-line treatment of MSI-H/dMMR metastatic colorectal cancer.
  • The combination immunotherapy represents a significant advancement for patients with this specific colorectal cancer subtype.