{
  "abstract": "Background Nivolumab plus ipilimumab (COMBO) is the standard treatment for asymptomatic melanoma brain metastases (MBM), but current guidelines do not provide specific recommendations for treatment discontinuation in responding patients. This study aimed to evaluate outcomes after COMBO discontinuation within 24 months and the role of continuing treatment beyond 24 months.Methods Patients with MBM treated with COMBO who discontinued treatment within 24 months for reasons other than disease progression or continued beyond this time point were retrieved. Overall survival (OS), objective response, progression-free survival (PFS) and toxicities were analyzed.Results 465 patients were included: 392 discontinued COMBO within 24 months, while 73 continued beyond 24 months. Treatment was discontinued due to complete response (CR, n=47), partial response (PR, n=45), stable disease (SD, n=12), toxicity after SD (n=59), toxicity after CR (n=99), or toxicity after PR (n=130). At multivariable analysis, the line of treatment (>first vs first: HR 2.65 (1.62–4.32)), the immune-related adverse events (irrespective of anti-tumor necrosis factor-alpha) (HR 0.18 (0.07–0.42)); COMBO discontinuation after CR (HR 0.15 (0.05–0.40)), or PR (HR 0.08 (0.03–0.26)), as well as stopping due to toxicity after CR (HR 0.14 (0.07–0.27)) or PR (HR 0.51 (0.32–0.82)), were associated with OS. Notably, at a median follow-up of 51 months (IQR 31–70), patients with CR/PR who discontinued COMBO within 24 months had PFS and OS comparable to those who continued treatment beyond this time point. 4-year OS exceeded 83% in patients discontinuing COMBO after CR, PR, or toxicity following CR, compared with 66.4% in those discontinuing due to toxicity after PR; median PFS was not reached in the former groups but was 18.6 months in the toxicity after PR group.Conclusion Discontinuation of COMBO within 24 months appears safe in patients with CR and in selected cases of PR, with no survival disadvantage versus prolonged therapy.",
  "authors": [
    {
      "affiliations": [
        "Unit of Medical Oncology, University of Perugia, Perugia, Italy"
      ],
      "name": "Mario Mandalà"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Monica F Chen"
    },
    {
      "affiliations": [
        "Mass General Brigham, Boston, Massachusetts, USA"
      ],
      "name": "Ryan J Sullivan"
    },
    {
      "affiliations": [
        "San Paolo Hospital, Bari, Apulia, Italy"
      ],
      "name": "Maria Chiara Sergi"
    },
    {
      "affiliations": [
        "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA",
        "Department of Medicine, Weill Cornell Medical College, New York, New York, USA"
      ],
      "name": "Michael Postow"
    },
    {
      "affiliations": [
        "Mass General Brigham, Boston, Massachusetts, USA"
      ],
      "name": "Aleigha R Lawless"
    },
    {
      "affiliations": [
        "Mass General Brigham, Boston, Massachusetts, USA"
      ],
      "name": "Derek Effiom"
    },
    {
      "affiliations": [
        "The Royal Marsden NHS Foundation Trust, London, UK"
      ],
      "name": "Tobias Peres"
    },
    {
      "affiliations": [
        "The University of Manchester, Manchester, England, UK"
      ],
      "name": "Paul C Lorigan"
    },
    {
      "affiliations": [
        "The University of Manchester, Manchester, England, UK"
      ],
      "name": "Patricio Serra-Bellver"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Zurich, Zürich, Switzerland"
      ],
      "name": "Reinhard Dummer"
    },
    {
      "affiliations": [
        "Dermato-Oncology, Eberhard Karls Universitat Tubingen, Tubingen, Germany",
        "ICANS, Strasbourg, Grand Est, France"
      ],
      "name": "Teresa Amaral"
    },
    {
      "affiliations": [
        "Department of Dermatology, Eberhard Karls Universitat Tubingen, Tübingen, Germany"
      ],
      "name": "Marie-Lena Rasch"
    },
    {
      "affiliations": [
        "Epidemiology and Biostatistics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy"
      ],
      "name": "Diana Giannarelli"
    },
    {
      "affiliations": [
        "National Cancer Institute IRCCS Pascale Foundation, Naples, Campania, Italy"
      ],
      "name": "Maria Grazia Vitale"
    },
    {
      "affiliations": [
        "Department of Oncology, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Hildur Helgadottir"
    },
    {
      "affiliations": [
        "Gustave Roussy, Villejuif, France"
      ],
      "name": "Caroline Robert"
    },
    {
      "affiliations": [
        "Unit of Medical Oncology, University of Perugia, Perugia, Italy"
      ],
      "name": "Martina Ubaldi"
    },
    {
      "affiliations": [
        "Vanderbilt University Medical Center, Nashville, Tennessee, USA"
      ],
      "name": "Douglas B Johnson"
    },
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Michele Del Vecchio"
    },
    {
      "affiliations": [
        "Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy"
      ],
      "name": "Alice Indini"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Utrecht University, Utrecht, Utrecht, Netherlands"
      ],
      "name": "Karijn P M Suijkerbuijk"
    },
    {
      "affiliations": [
        "Mount Vernon Cancer Centre, Northwood, UK"
      ],
      "name": "Paul Nathan"
    },
    {
      "affiliations": [
        "Mount Vernon Cancer Centre, Northwood, UK"
      ],
      "name": "Thomas Carter"
    },
    {
      "affiliations": [
        "Medische Oncologie, Vrije Universiteit Brussel, Brussels, Brussels, Belgium"
      ],
      "name": "Bart Neyns"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Brussels, Belgium"
      ],
      "name": "Iris Dirven"
    },
    {
      "affiliations": [
        "Melanoma Institute Australia, North Sydney, New South Wales, Australia",
        "Champalimaud Foundation, Lisbon, Lisbon, Portugal"
      ],
      "name": "Ines Pires da Silva"
    },
    {
      "affiliations": [
        "Melanoma Institute Australia, North Sydney, New South Wales, Australia"
      ],
      "name": "Alexander Maxwell Menzies"
    },
    {
      "affiliations": [
        "Dermatology, University of Duisburg-Essen, Essen, Germany"
      ],
      "name": "Lisa Zimmer"
    },
    {
      "affiliations": [
        "Dermatology, University of Duisburg-Essen, Essen, Germany"
      ],
      "name": "Elisabeth Livingstone"
    },
    {
      "affiliations": [
        "Department of Oncology, Hematology, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Roberta Depenni"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Schleswig Holstein, Kiel, Germany"
      ],
      "name": "Katharina Kähler"
    },
    {
      "affiliations": [
        "Department of Dermatology, University Hospital Schleswig Holstein, Kiel, Germany"
      ],
      "name": "Axel Hauschild"
    },
    {
      "affiliations": [
        "Genoa National Institute for Cancer Research, Genoa, Liguria, Italy"
      ],
      "name": "Francesco Spagnolo"
    },
    {
      "affiliations": [
        "University of Siena, Siena, Italy"
      ],
      "name": "Anna Maria Di Giacomo"
    },
    {
      "affiliations": [
        "Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain"
      ],
      "name": "Ana Arance"
    },
    {
      "affiliations": [
        "Unit of Medical Oncology, Department of Oncology and Hematology, ASST Papa Giovanni XXIII, Bergamo, Lombardia, Italy"
      ],
      "name": "Barbara Merelli"
    },
    {
      "affiliations": [
        "Dermatologic Clinic, Department of Medical Sciences, University of Turin, Torino, Piemonte, Italy"
      ],
      "name": "Pietro Quaglino"
    },
    {
      "affiliations": [
        "Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Lazio, Italy",
        "Università Cattolica del Sacro Cuore - Campus di Roma, Rome, Lazio, Italy"
      ],
      "name": "Ernesto Rossi"
    },
    {
      "affiliations": [
        "Medical Oncology Unit, University of Bari, Policlinico Hospital of Bari, Bari, Puglia, Italy",
        "IRCCS Ospedale Oncologico di Bari Giovanni Paolo II, Bari, Italy"
      ],
      "name": "Marco Tucci"
    },
    {
      "affiliations": [
        "Oncology Department, Giovanni Paolo II Cancer Institute IRCCS, Bari, Apulia, Italy"
      ],
      "name": "Michele Guida"
    },
    {
      "affiliations": [
        "Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain"
      ],
      "name": "Eva Muñoz-Couselo"
    },
    {
      "affiliations": [
        "Melanoma Institute Australia, Wollstonecraft, New South Wales, Australia"
      ],
      "name": "Georgina V Long"
    },
    {
      "affiliations": [
        "The Royal Marsden NHS Foundation Trust, London, UK"
      ],
      "name": "James Larkin"
    },
    {
      "affiliations": [
        "Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy",
        "Federico II University Hospital, Naples, Campania, Italy"
      ],
      "name": "Paolo A Ascierto"
    }
  ],
  "title": "Discontinuation of combo immunotherapy and outcome of patients with melanoma brain metastases",
  "uid": "6b960901-dbb8-563f-afce-785b7a3f6a59"
}