A Single-Arm Phase 2 Trial of Trametinib in Patients with Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.

Autor:	Schuetze SM; University of Michigan, Ann Arbor, Michigan., Ballman KV; Mayo Clinic, Rochester, Minnesota., Heise R; Weill Cornell Medicine, New York, New York., Ganjoo KN; Stanford University Medical Center, Stanford, California., Davis EJ; Vanderbilt University Medical Center, Nashville, Tennessee., George S; Dana Farber Cancer Institute, Boston, Massachusetts., Burgess MA; University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania., Choy E; Massachusetts General Hospital, Boston, Massachusetts., Shepard DR; Cleveland Clinic, Cleveland, Ohio., Tinoco G; The Ohio State University, Columbus, Ohio., Hirbe A; Washington Univeristy in St. Louis, St. Louis, Missouri., Kelly CM; Memorial Sloan Kettering Cancer Center, New York, New York., Attia S; Mayo Clinic, Jacksonville, Florida., Deshpande HA; Yale Cancer Center, New Haven, Connecticut., Schwartz GK; Case Comprehensive Cancer Center, Cleveland, Ohio., Siontis BL; Mayo Clinic, Rochester, Minnesota., Riedel RF; Duke Cancer Institute, Durham, North Carolina., von Mehren M; Fox Chase Cancer Center, Philadelphia, Pennsylvania., Kozlowski E; SARC, Ann Arbor, Michigan., Chen HX; National Cancer Institute, Rockville, Maryland., Astbury C; Cleveland Clinic, Cleveland, Ohio., Rubin BP; Cleveland Clinic, Cleveland, Ohio.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Oct 15; Vol. 30 (20), pp. 4584-4592.
DOI:	10.1158/1078-0432.CCR-23-3817
Abstrakt:	Purpose: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 (calmodulinbinding transcription activator 1) operating as an oncogenic driver through activation of the MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE. Patients and Methods: A phase 2 trial of trametinib was conducted in patients with locally advanced or metastatic EHE. Eligibility requirements included evidence of tumor progression or presence of EHE-related pain requiring opiates for management before enrollment. The primary endpoint was objective response rate (ORR) as per RECIST1.1 in cases with TAZ- CAMTA1 confirmed by fusion-FISH. Secondary objectives were to estimate ORR for all patients, median progression-free survival (PFS), 2-year overall survival (OS) rate, patient safety, and change in patient-reported global health and pain scores per PROMIS questionnaires. Results: 44 patients enrolled and 42 started trametinib. TAZ- CAMTA1 was detected in 27 tumor samples. TheORRwas 3.7%[95% confidence interval (CI), 0.094-19.0], median PFS was 10.4 months (95%CI, 7.1-NA), and 2-year OS rate was 33.3%(95%CI, 19.1-58.2) in the target population. Median pain intensity and interference scores improved significantly after 4 weeks of trametinib in patients using opiates. Common adverse events related to trametinib were rash, fatigue, nausea/vomiting, diarrhea/constipation, alopecia, and edema; one grade 5 ARDS/pneumonitis was related to trametinib. Conclusions: Trametinib was associated with reduction in EHE-related pain and median PFS of more than 6 months, providing palliative benefit in patients with advanced EHE, but the trial did not meet the ORR goal. See related commentary by Van Tine and Haarberg, p. 4552. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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