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@ARTICLE{Grimm:274133,
      author       = {M.-O. Grimm and C. B. Grün and G. Niegisch and M. Pichler
                      and F. Roghmann and B. Schmitz-Dräger and G. Baretton and
                      M. Schmitz$^*$ and C. Bolenz and S. Foller and K. Leucht and
                      U. Schumacher and M. Schostak and J. Meran and W. Loidl and
                      F. Zengerling},
      title        = {{T}ailored immunotherapy approach with nivolumab with or
                      without ipilimumab in patients with advanced transitional
                      cell carcinoma after platinum-based chemotherapy
                      ({TITAN}-{TCC}): a multicentre, single-arm, phase 2 trial.},
      journal      = {The lancet / Oncology},
      volume       = {24},
      number       = {4},
      issn         = {1470-2045},
      address      = {London},
      publisher    = {The Lancet Publ. Group},
      reportid     = {DKFZ-2023-00443},
      pages        = {347-359},
      year         = {2023},
      note         = {2023 Apr;24(4):347-359},
      abstract     = {Nivolumab is used after platinum-based chemotherapy in
                      patients with metastatic urothelial carcinoma. Studies
                      suggest improved outcomes for dual checkpoint inhibition
                      with high ipilimumab doses. We aimed to examine the safety
                      and activity of nivolumab induction and high-dose ipilimumab
                      as an immunotherapeutic boost as a second-line treatment for
                      patients with metastatic urothelial carcinoma.TITAN-TCC is a
                      multicentre, single-arm, phase 2 trial done at 19 hospitals
                      and cancer centres in Germany and Austria. Adults aged 18
                      years or older with histologically confirmed metastatic or
                      surgically unresectable urothelial cancer of the bladder,
                      urethra, ureter, or renal pelvis were eligible. Patients had
                      to have progression during or after first-line
                      platinum-based chemotherapy and up to one more second-line
                      or third-line treatment, a Karnofsky Performance Score of 70
                      or higher, and measurable disease as per Response Evaluation
                      Criteria in Solid Tumors version 1.1. After four doses of
                      intravenous nivolumab 240 mg induction monotherapy every 2
                      weeks, patients with a partial or complete response at week
                      8 continued maintenance nivolumab, whereas those with stable
                      or progressive disease (non-responders) at week 8 received a
                      boost of two or four doses of intravenous nivolumab 1 mg/kg
                      plus ipilimumab 3 mg/kg every 3 weeks. Patients who
                      subsequently had progressive disease during nivolumab
                      maintenance also received a boost, using this schedule. The
                      primary endpoint was the confirmed investigator-assessed
                      objective response rate in the intention-to-treat population
                      and had to exceed $20\%$ for the null hypothesis to be
                      rejected (based on the objective response rate with
                      nivolumab monotherapy in the CheckMate-275 phase 2 trial).
                      This study is registered with ClinicalTrials.gov,
                      NCT03219775, and is ongoing.Between April 8, 2019, and Feb
                      15, 2021, 83 patients with metastatic urothelial carcinoma
                      were enrolled and all received nivolumab induction treatment
                      (intention-to-treat population). The median age of enrolled
                      patients was 68 years (IQR 61-76), and 57 $(69\%)$ were male
                      and 26 $(31\%)$ were female. 50 $(60\%)$ patients received
                      at least one boost dose. A confirmed investigator-assessed
                      objective response was recorded in 27 $(33\%)$ of 83
                      patients in the intention-to-treat population, including six
                      $(7\%)$ patients who had a complete response. This objective
                      response rate was significantly higher than the prespecified
                      threshold of $20\%$ or less $(33\%$ $[90\%$ CI 24-42];
                      p=0·0049). The most common grade 3-4 treatment-related
                      adverse events were immune-mediated enterocolitis (nine
                      $[11\%]$ patients) and diarrhoea (five $[6\%]$ patients).
                      Two $(2\%)$ treatment-related deaths were reported, both due
                      to immune-mediated enterocolitis.Treatment with nivolumab
                      and nivolumab plus ipilimumab boosts in early non-responders
                      and patients who progress late significantly improved
                      objective response rate after previous platinum-based
                      chemotherapy compared with the rate reported with nivolumab
                      in the CheckMate-275 trial. Our study provides evidence for
                      the added value of high-dose ipilimumab 3 mg/kg and suggests
                      a potential role for the combination as a rescue strategy in
                      platinum-pretreated patients with metastatic urothelial
                      carcinoma.Bristol Myers Squibb.},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36868252},
      doi          = {10.1016/S1470-2045(23)00053-0},
      url          = {https://inrepo02.dkfz.de/record/274133},
}