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@ARTICLE{Livingstone:277708,
      author       = {E. Livingstone$^*$ and H. Gogas and L. Kandolf-Sekulovic
                      and F. Meier and T. K. Eigentler and M. Ziemer and P. A. M.
                      Terheyden and A. H. Gesierich and R. A. Herbst and K. C.
                      Kähler and D. C. Ziogas and Z. Mijuskovic and M. Garzarolli
                      and C. Garbe and A. Roesch$^*$ and S. Ugurel$^*$ and R.
                      Gutzmer and J. J. Grob and F. Kiecker and J. Utikal$^*$ and
                      C. Windemuth-Kieselbach and S. Eckhardt and L. Zimmer$^*$
                      and D. Schadendorf$^*$},
      title        = {{E}arly switch from run-in treatment with vemurafenib plus
                      cobimetinib to atezolizumab after 3 months leads to rapid
                      loss of tumour control in patients with advanced
                      {BRAFV}600-positive melanoma: {T}he {I}mmuno{C}obi{V}em
                      phase 2 randomised trial.},
      journal      = {European journal of cancer},
      volume       = {190},
      issn         = {0014-2964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2023-01425},
      pages        = {112941},
      year         = {2023},
      abstract     = {ImmunoCobiVem investigated whether a planned switch to
                      atezolizumab after achieving tumour control during run-in
                      with vemurafenib + cobimetinib improves progression-free
                      survival (PFS) and overall survival (OS) compared to
                      continuous targeted therapy (TT) in patients with previously
                      untreated advanced BRAFV600-mutated melanoma.In this
                      multicenter phase 2 study, patients received vemurafenib
                      plus cobimetinib. After 3months, patients without
                      progressive disease (PD) were randomly assigned (1:1) to
                      continue vemurafenib + cobimetinib (Arm A) or switch to
                      atezolizumab (Arm B) until first documented PD (PD1).
                      Primary outcome was PFS1 (time from start of run-in until
                      PD1 or death). OS and safety were also assessed.Of 185
                      patients enroled between November 2016 and December 2019,
                      135 were randomly assigned after the run-in period (Arm A, n
                      = 69; Arm B, n = 66). Median PFS1 was significantly longer
                      in Arm A versus Arm B (13.9 versus 5.9months; hazard ratio
                      [HR] 0.55; $95\%$ confidence interval [CI], 0.37-0.84;
                      PStratified=0.001). Median OS was not reached in either arm
                      (HR 1.22; $95\%CI,$ 0.69-2.16; PStratified=0.389); 2-year OS
                      was higher in Arm B versus Arm A $(67\%;$ $95\%CI,$ 53-78
                      versus $58\%;$ $95\%CI,$ 45-70). Grade 3/4 AEs occurred in
                      $55\%$ of patients in Arm A and $64\%$ in Arm B;
                      treatment-related AEs led to discontinuation of any drug in
                      $7\%$ and $9\%$ of patients, respectively.In patients with
                      BRAFV600-mutated advanced melanoma who achieve tumour
                      control with TT, early switch at 3months to atezolizumab led
                      to rapid loss of tumour control but provided a numerical OS
                      benefit at 2years compared with continued TT.},
      keywords     = {Checkpoint inhibition (Other) / First-line (Other) /
                      Melanoma (Other) / Run-in (Other) / Sequence (Other) /
                      Targeted therapy (Other)},
      cin          = {ED01 / A370},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331 / 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:37482012},
      doi          = {10.1016/j.ejca.2023.112941},
      url          = {https://inrepo02.dkfz.de/record/277708},
}