A Single Arm Phase 2 Trial of Trametinib in Patients With Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.
Clin Cancer Res
; 2024 Mar 06.
Article
en En
| MEDLINE
| ID: mdl-38446990
ABSTRACT
PURPOSE:
Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 operating as an oncogenic driver through activation of 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 ANDMETHODS:
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 prior to enrollment. The primary endpoint was objective response rate (ORR) per RECIST1.1 in cases with TAZ-CAMTA1 confirmed by fusion-FISH. Secondary objectives were to estimate ORR for all patients, median PFS, 2-year 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. The ORR was 3.7% (95% 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 AEs 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Clin Cancer Res
/
Clin. cancer res
/
Clinical cancer research
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos