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@ARTICLE{Becker:277747,
      author       = {J. Becker$^*$ and S. Ugurel$^*$ and U. Leiter$^*$ and F.
                      Meier$^*$ and R. Gutzmer and S. Haferkamp and L. Zimmer and
                      E. Livingstone$^*$ and T. K. Eigentler and A. Hauschild and
                      F. Kiecker and J. C. Hassel$^*$ and P. Mohr and M. Fluck and
                      I. Thomas and M. Garzarolli and I. Grimmelmann and K.
                      Drexler and A. N. Spillner and S. Eckhardt and D.
                      Schadendorf$^*$},
      collaboration = {DeCOG},
      othercontributors = {A. van Akkoi and W. van Houdt and T. Wilhelm and K. Farmer
                          and C. Ulrich and T. Gambichler and L. Bluhm and H. Schinagl
                          and I. Kellner and R. Herbst and F. Meiß and D.
                          Rafei-Shamsabadi and S. Sell and M. Kaatz and L. Wulfken and
                          M. Hartmann and K. Kähler and M. Ziemer and J. Simon and P.
                          Terheyden and D. Thaci and C. Loquai and H. Mitzel-Rink and
                          S. Grabbe and H. Stege and M. Gaiser$^*$ and J. Utikal$^*$
                          and C. Berking and L. Heinzerling and M. Schlaak and D.
                          Tomsitz and J. Dyballa and N. Magnolo and C. Weishaupt and
                          M. Berneburg and C. Garbe and L. Flatz and A. Gesierich and
                          B. Schilling},
      title        = {{A}djuvant immunotherapy with nivolumab versus observation
                      in completely resected {M}erkel cell carcinoma
                      ({ADMEC}-{O}): disease-free survival results from a
                      randomised, open-label, phase 2 trial.},
      journal      = {The lancet},
      volume       = {402},
      number       = {10404},
      issn         = {0140-6736},
      address      = {London [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2023-01464},
      pages        = {798-808},
      year         = {2023},
      note         = {2023 Sep 2;402(10404):798-808},
      abstract     = {Merkel cell carcinoma (MCC) is an immunogenic but
                      aggressive skin cancer. Even after complete resection and
                      radiation, relapse rates are high. PD-1 and PD-L1 checkpoint
                      inhibitors showed clinical benefit in advanced MCC. We aimed
                      to assess efficacy and safety of adjuvant immune checkpoint
                      inhibition in completely resected MCC (ie, a setting without
                      an established systemic standard-of-care treatment).In this
                      multicentre phase 2 trial, patients (any stage, Eastern
                      Cooperative Oncology Group performance status 0-1) at 20
                      academic medical centres in Germany and the Netherlands with
                      completely resected MCC lesions were randomly assigned 2:1
                      to receive nivolumab 480 mg every 4 weeks for 1 year, or
                      observation, stratified by stage (American Joint Committee
                      on Cancer stages 1-2 vs stages 3-4), age (<65 vs ≥65
                      years), and sex. Landmark disease-free survival (DFS) at 12
                      and 24 months was the primary endpoint, assessed in the
                      intention-to-treat populations. Overall survival and safety
                      were secondary endpoints. This planned interim analysis was
                      triggered when the last-patient-in was followed up for more
                      than 1 year. This study is registered with
                      ClinicalTrials.gov (NCT02196961) and with the EU Clinical
                      Trials Register (2013-000043-78).Between Oct 1, 2014, and
                      Aug 31, 2020, 179 patients were enrolled (116 $[65\%]$ stage
                      3-4, 122 $[68\%]$ ≥65 years, 111 $[62\%]$ male).
                      Stratification factors (stage, age, sex) were balanced
                      across the nivolumab (n=118) and internal control group
                      (observation, n=61); adjuvant radiotherapy was more common
                      in the control group. At a median follow-up of 24·3 months
                      (IQR 19·2-33·4), median DFS was not reached
                      (between-groups hazard ratio 0·58, $95\%$ CI 0·30-1·12);
                      DFS rates in the nivolumab group were $85\%$ at 12 months
                      and $84\%$ at 24 months, and in the observation group were
                      $77\%$ at 12 months and $73\%$ at 24 months. Overall
                      survival results were not yet mature. Grade 3-4 adverse
                      events occurred in 48 $[42\%]$ of 115 patients who received
                      at least one dose of nivolumab and seven $[11\%]$ of 61
                      patients in the observation group. No treatment-related
                      deaths were reported.Adjuvant therapy with nivolumab
                      resulted in an absolute risk reduction of $9\%$ (1-year DFS)
                      and $10\%$ (2-year DFS). The present interim analysis of
                      ADMEC-O might suggest clinical use of nivolumab in this area
                      of unmet medical need. However, overall survival events
                      rates, with ten events in the active treatment group and six
                      events in the half-the-size observation group, are not
                      mature enough to draw conclusions. The explorative data of
                      our trial support the continuation of ongoing, randomised
                      trials in this area. ADMEC-O suggests that adjuvant
                      immunotherapy is clinically feasible in this area of unmet
                      medical need.Bristol Myers Squibb.},
      cin          = {ED01 / TU01 / DD01 / HD01 / A370},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331 / I:(DE-He78)TU01-20160331 /
                      I:(DE-He78)DD01-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)A370-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37451295},
      doi          = {10.1016/S0140-6736(23)00769-9},
      url          = {https://inrepo02.dkfz.de/record/277747},
}