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Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial.
DeAngelo, Daniel J; Radia, Deepti H; George, Tracy I; Robinson, William A; Quiery, Albert T; Drummond, Mark W; Bose, Prithviraj; Hexner, Elizabeth O; Winton, Elliott F; Horny, Hans-Peter; Tugnait, Meera; Schmidt-Kittler, Oleg; Evans, Erica K; Lin, Hui-Min; Mar, Brenton G; Verstovsek, Srdan; Deininger, Michael W; Gotlib, Jason.
Afiliação
  • DeAngelo DJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. daniel_deangelo@dfci.harvard.edu.
  • Radia DH; Guy's & St Thomas' NHS Foundation Trust, London, UK.
  • George TI; ARUP Laboratories, University of Utah, Salt Lake City, UT, USA.
  • Robinson WA; University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Quiery AT; University of Michigan, Ann Arbor, MI, USA.
  • Drummond MW; Beatson Cancer Centre, Glasgow, UK.
  • Bose P; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hexner EO; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
  • Winton EF; Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
  • Horny HP; Institute of Pathology, Ludwig-Maximilians University, Munich, Germany.
  • Tugnait M; Blueprint Medicines Corporation, Cambridge, MA, USA.
  • Schmidt-Kittler O; Blueprint Medicines Corporation, Cambridge, MA, USA.
  • Evans EK; Blueprint Medicines Corporation, Cambridge, MA, USA.
  • Lin HM; Blueprint Medicines Corporation, Cambridge, MA, USA.
  • Mar BG; Blueprint Medicines Corporation, Cambridge, MA, USA.
  • Verstovsek S; The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Deininger MW; Versiti Blood Research Institute and Division Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Gotlib J; Stanford University School of Medicine and Stanford Cancer Institute, Stanford, CA, USA.
Nat Med ; 27(12): 2183-2191, 2021 12.
Article em En | MEDLINE | ID: mdl-34873347
Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study ( NCT02561988 ) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30-400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets <50 × 109/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Pirróis / Triazinas / Mastocitose Sistêmica Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirazóis / Pirróis / Triazinas / Mastocitose Sistêmica Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article