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@ARTICLE{Ascierto:277858,
      author       = {P. A. Ascierto and R. Dummer and H. J. Gogas and A. Arance
                      and M. Mandala and G. Liszkay and C. Garbe and D.
                      Schadendorf$^*$ and I. Krajsova and R. Gutzmer and V.
                      Chiarion-Sileni and C. Dutriaux and J. W. B. de Groot and N.
                      Yamazaki and C. Loquai and C. Robert and K. T. Flaherty},
      title        = {{C}ontribution of {MEK} {I}nhibition to {BRAF}/{MEK}
                      {I}nhibitor {C}ombination {T}reatment of {BRAF}-{M}utant
                      {M}elanoma: {P}art 2 of the {R}andomized, {O}pen-{L}abel,
                      {P}hase {III} {COLUMBUS} {T}rial.},
      journal      = {Journal of clinical oncology},
      volume       = {41},
      number       = {29},
      issn         = {0732-183X},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2023-01526},
      pages        = {4621-4631},
      year         = {2023},
      note         = {2023 Oct 10;41(29):4621-4631},
      abstract     = {In COLUMBUS part 1, patients with advanced BRAFV600-mutant
                      melanoma were randomly assigned 1:1:1 to encorafenib 450 mg
                      once daily plus binimetinib 45 mg twice a day (COMBO450),
                      vemurafenib 960 mg twice a day, or encorafenib 300 mg once
                      daily (ENCO300). As previously reported, COMBO450 improved
                      progression-free survival (PFS) versus vemurafenib (part 1
                      primary end point) and ENCO300 (part 1 key secondary end
                      point; not statistically significant). Part 2, requested by
                      the US Food and Drug Administration, evaluated the
                      contribution of binimetinib by maintaining the same
                      encorafenib dosage in the combination (encorafenib 300 mg
                      once daily plus binimetinib 45 mg twice daily [COMBO300])
                      and ENCO300 arms.In part 2, patients were randomly assigned
                      3:1 to COMBO300 or ENCO300. ENCO300 (parts 1 and 2) data
                      were combined, per protocol, for PFS analysis (key secondary
                      end point) by a blinded independent review committee (BIRC).
                      Other analyses included overall response rate (ORR), overall
                      survival, and safety.Two hundred fifty-eight patients
                      received COMBO300, and 86 received ENCO300. Per protocol,
                      ENCO300 arms (parts 1 and 2 combined) were also evaluated (n
                      = 280). The median follow-up for ENCO300 was 40.8 months
                      (part 1) and 57.1 months (part 2). The median PFS $(95\%$
                      CI) was 12.9 months (10.9 to 14.9) for COMBO300 versus 9.2
                      months (7.4 to 11.1) for ENCO300 (parts 1 and 2) and 7.4
                      months (5.6 to 9.2) for ENCO300 (part 2). The hazard ratio
                      $(95\%$ CI) for COMBO300 was 0.74 (0.60 to 0.92; two-sided P
                      = .003) versus ENCO300 (parts 1 and 2). The ORR by BIRC
                      $(95\%$ CI) was $68\%$ (62 to 74) and $51\%$ (45 to 57) for
                      COMBO300 and ENCO300 (parts 1 and 2), respectively. COMBO300
                      had greater relative dose intensity and fewer grade 3/4
                      adverse events than ENCO300.COMBO300 improved PFS, ORR, and
                      tolerability compared with ENCO300, confirming the
                      contribution of binimetinib to efficacy and safety.},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37506329},
      doi          = {10.1200/JCO.22.02322},
      url          = {https://inrepo02.dkfz.de/record/277858},
}