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@ARTICLE{Isgandarov:271268,
      author       = {A. Isgandarov$^*$ and C. Darr$^*$ and P. Posdzich$^*$ and
                      K. Hermann$^*$ and B. A. Hadaschik$^*$ and V. Grünwald$^*$},
      title        = {{N}ew treatment approaches for and ongoing trials in
                      metastatic hormone-sensitive prostate cancer.[{N}eue
                      {T}herapieansätze und {S}tudienübersicht beim
                      metastasierten hormonsensitiven {P}rostatakarzinom.]},
      journal      = {Die Urologie},
      volume       = {62},
      number       = {4},
      issn         = {2731-7064},
      address      = {New York},
      publisher    = {Springer Medizin},
      reportid     = {DKFZ-2023-00400},
      pages        = {369-375},
      year         = {2023},
      note         = {2023 Apr;62(4):369-375},
      abstract     = {For many years, therapy for metastatic hormone-sensitive
                      prostate cancer (mHSPC) was dominated by monotherapy using
                      androgen deprivation therapy (ADT). With the demonstration
                      of survival benefit with intensified systemic therapy from
                      the CHAARTED and STAMPEDE trials, this has fundamentally
                      changed. We analyzed the phase III trials that led to the
                      change in therapy in mHSPC. In addition, we summarized
                      ongoing trials in mHSPC.The ongoing studies and current data
                      on systemic therapy in mHSPC were analyzed.Monotherapy with
                      ADT is no longer considered the standard therapy for mHSPC.
                      Combination therapy with ADT and novel androgen receptor
                      targeting agents (ARTAs: abiraterone, apalutamide,
                      enzalutamide) is now the established standard option. The
                      added value of further intensification of therapy was
                      demonstrated in the first trials of triple therapy with ADT
                      + docetaxel + darolutamide or abiraterone in mHSPC. Current
                      studies are also investigating new forms of therapy.
                      Lutetium177-PSMA radioligand therapy is an established
                      standard in metastatic castration-resistant prostate cancer
                      (mCRPC) and is currently being evaluated in combination with
                      ADT + ARTA in mHSPC. The use of PARP inhibitors (PARPi) have
                      been established in mCRPC. Current studies are showing early
                      evidence of benefit from novel combination therapies of
                      PARPi + ARTA, which represent a further expansion of the
                      therapeutic landscape. Experimental therapies are testing
                      another combination, such as an AKT inhibitor with ARTA in
                      patients with PTEN (phosphatase and tensin homolog) loss.
                      Based on the proof of principle in mCRPC, this combination
                      is now being evaluated in earlier stage mHSPC. Other
                      experimental therapies in clinical testing include
                      inhibitors of cyclin dependent kinases (CDK).Combination
                      therapies are the current standard of care for mHSPC, with
                      the combination of ADT + ARTA dominating. Preliminary
                      results underline the importance of further intensification
                      of therapy by means of triple therapy. However, novel
                      combinations with radioligand therapy or PARP inhibitors are
                      also promising in the treatment of mHSPC. Preliminary
                      results show the principle efficacy of AKT inhibitors in
                      patients with PTEN loss, which similar to therapy with
                      CDK4/6 inhibitors still have to prove their clinical
                      relevance in randomized trials.},
      subtyp        = {Review Article},
      keywords     = {AKT (Other) / Androgen receptor (Other) / CDK4/6 (Other) /
                      PARP (Other) / Radioligand therapy (Other)},
      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:36823372},
      doi          = {10.1007/s00120-023-02046-z},
      url          = {https://inrepo02.dkfz.de/record/271268},
}