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Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.
Chalabi, Myriam; Verschoor, Yara L; Tan, Pedro Batista; Balduzzi, Sara; Van Lent, Anja U; Grootscholten, Cecile; Dokter, Simone; Büller, Nikè V; Grotenhuis, Brechtje A; Kuhlmann, Koert; Burger, Jacobus W; Huibregtse, Inge L; Aukema, Tjeerd S; Hendriks, Eduard R; Oosterling, Steven J; Snaebjornsson, Petur; Voest, Emile E; Wessels, Lodewyk F; Beets-Tan, Regina G; Van Leerdam, Monique E; Schumacher, Ton N; van den Berg, José G; Beets, Geerard L; Haanen, John B.
Afiliação
  • Chalabi M; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Verschoor YL; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Tan PB; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Balduzzi S; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Van Lent AU; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Grootscholten C; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Dokter S; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Büller NV; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Grotenhuis BA; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Kuhlmann K; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Burger JW; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Huibregtse IL; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Aukema TS; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Hendriks ER; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Oosterling SJ; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Snaebjornsson P; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Voest EE; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Wessels LF; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Beets-Tan RG; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Van Leerdam ME; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Schumacher TN; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • van den Berg JG; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Beets GL; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
  • Haanen JB; From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and
N Engl J Med ; 390(21): 1949-1958, 2024 Jun 06.
Article em En | MEDLINE | ID: mdl-38838311
ABSTRACT

BACKGROUND:

Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited.

METHODS:

We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., ≤2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses.

RESULTS:

Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had recurrence of disease.

CONCLUSIONS:

In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.).
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Colon_e_reto Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Neoplasias do Colo / Terapia Neoadjuvante / Reparo de Erro de Pareamento de DNA / Ipilimumab / Antineoplásicos Imunológicos / Nivolumabe Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: N Engl J Med / N. Engl. j. med / New England journal of medicine Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Colon_e_reto Base de dados: MEDLINE Assunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Neoplasias do Colo / Terapia Neoadjuvante / Reparo de Erro de Pareamento de DNA / Ipilimumab / Antineoplásicos Imunológicos / Nivolumabe Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: N Engl J Med / N. Engl. j. med / New England journal of medicine Ano de publicação: 2024 Tipo de documento: Article