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@ARTICLE{Leachman:309929,
      author       = {S. A. Leachman and J. J. Luke and P. A. Ascierto and G. V.
                      Long and M. A. Khattak and P. Rutkowski and Z. J. Xu and M.
                      Fukunaga-Kalabis and C. Krepler and A. M. M. Eggermont$^*$
                      and D. Schadendorf$^*$},
      title        = {{A}djuvant {P}embrolizumab for {S}tage {IIB} or {IIC}
                      {M}elanoma: {A} {S}econdary {A}nalysis of a {R}andomized
                      {C}linical {T}rial.},
      journal      = {JAMA network open},
      volume       = {9},
      number       = {2},
      issn         = {2574-3805},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DKFZ-2026-00379},
      pages        = {e2559603},
      year         = {2026},
      note         = {#DKTKZFB9# / #NCTZFB9#},
      abstract     = {Patients with melanoma are at risk of developing subsequent
                      cutaneous malignant neoplasms, and the effect of prior
                      immunotherapy is unknown.To analyze new skin cancers in
                      participants with high-risk stage II melanoma treated with
                      adjuvant pembrolizumab or placebo.The multicenter
                      double-blind, phase 3 KEYNOTE-716 randomized clinical trial
                      enrolled 976 participants 12 years or older with completely
                      resected stage IIB or IIC cutaneous melanoma between
                      September 23, 2018, and November 4, 2020. Follow-up was
                      completed on February 16, 2024. This analysis was not
                      prespecified in the trial protocol.Participants were
                      randomly assigned to receive intravenous pembrolizumab, 200
                      mg (2 mg/kg for pediatric participants), or placebo, every 3
                      weeks for no more than 17 cycles.Secondary analyses of
                      incidence and time to diagnosis of new melanoma or other
                      cutaneous malignant neoplasm, sensitivity analysis of
                      recurrence-free survival (RFS) with new primary melanoma
                      counted as an event, and incidence of immune-mediated severe
                      skin reactions.A total of 976 participants were assigned to
                      treatment (487 to pembrolizumab and 489 to placebo), of whom
                      589 $(60.3\%)$ were male (median age at diagnosis, 61 [IQR,
                      52-69] years). The median follow-up was 52.8 (range,
                      39.4-64.8) months. In the pembrolizumab group, 37
                      participants $(7.6\%)$ were diagnosed with new skin cancers
                      (median time to diagnosis, 168.0 [range, 1.0-1182.0] days);
                      12 $(2.5\%)$ had new invasive primary melanoma, 6 $(1.2\%)$
                      had new primary melanoma in situ, 19 $(3.9\%)$ had basal
                      cell carcinoma (BCC), and 9 $(1.8\%)$ had cutaneous squamous
                      cell carcinoma (cSCC). In the placebo group, 56 participants
                      $(11.5\%)$ were diagnosed with new skin cancers (median time
                      to diagnosis, 177.0 [range, 1.0-1043.0] days); 9 $(1.8\%)$
                      had new invasive primary melanoma, 9 $(1.8\%)$ had new
                      primary melanoma in situ, 26 $(5.3\%)$ had BCC, and 17
                      $(3.5\%)$ had cSCC. Median RFS with new primary melanoma
                      counted as an event was not reached with pembrolizumab and
                      was 59.2 months $(95\%$ CI, 53.9 months to not reached) with
                      placebo (hazard ratio, 0.65; $95\%$ CI, 0.52-0.80); 48-month
                      RFS was $68.7\%$ and $56.5\%,$ respectively. Immune-mediated
                      severe skin reactions occurred in 16 of 483 participants
                      $(3.3\%)$ in the pembrolizumab group and 3 of 486 $(0.6\%)$
                      in the placebo group (grade 3 or 4: 14 $[2.9\%]$ vs 3
                      $[0.6\%]).In$ this secondary analysis of a randomized
                      clinical trial, the incidence of new primary melanoma was
                      not different between groups, whereas nonmelanoma skin
                      cancers were more common with placebo. The RFS benefit of
                      pembrolizumab remained after accounting for new primary
                      melanomas. Immune-mediated severe skin reactions occurred
                      infrequently and were manageable. These findings support the
                      use of adjuvant pembrolizumab in high-risk stage II
                      melanoma.ClinicalTrials.gov Identifier: NCT03553836.},
      keywords     = {Humans / Antibodies, Monoclonal, Humanized: therapeutic use
                      / Antibodies, Monoclonal, Humanized: administration $\&$
                      dosage / Melanoma: drug therapy / Melanoma: pathology / Male
                      / Female / Middle Aged / Skin Neoplasms: drug therapy / Skin
                      Neoplasms: pathology / Double-Blind Method / Aged /
                      Antineoplastic Agents, Immunological: therapeutic use /
                      Adult / Chemotherapy, Adjuvant / Neoplasm Staging /
                      Antibodies, Monoclonal, Humanized (NLM Chemicals) /
                      pembrolizumab (NLM Chemicals) / Antineoplastic Agents,
                      Immunological (NLM Chemicals)},
      cin          = {ED01 / WT01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331 / I:(DE-He78)WT01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41701495},
      doi          = {10.1001/jamanetworkopen.2025.59603},
      url          = {https://inrepo02.dkfz.de/record/309929},
}