A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma.

ABSTRACT:

Background

Patients with recurrent/metastatic uterine leiomyosarcoma (U-LMS) have a dismal prognosis. This phase II study aims to evaluate trabectedin efficacy and safety in advanced U-LMS.

Methods

Eligible patients had received???one line of chemotherapy. Gemcitabine?±?docetaxel naive patients were randomised to Arm A: trabectedin 1.3?mg/m² or calibration Arm B: gemcitabine 900?mg/m² and docetaxel 75?mg/m². Patients who had already received gemcitabine?±?docetaxel directly entered Arm A. Primary end-point: 6-month progression-free rate (PFS-6). The null hypothesis that the true PFS-6?=?14% was tested against a one-sided alternative. This design yielded a 5% type I error rate and 90% power when the true PFS-6 is 25%.

Results

Overall, 126 patients entered Arm A (45 from randomisation and 81 directly) and 42 Arm B. Arm A patients characteristics: median age?=?57; ?2 previous chemotherapy lines?=?37.4%; metastatic disease?=?93%. The study met the condition for trabectedin activity: PFS-6?=?35.2% (95% CI: 26.2-45). No difference in PFS by the number of previous chemotherapy lines emerged. Median OS?=?20.6 months (IQR: 8-36.4). In Arm B, the PFS-6?=?51.5% (95% CI: 33.5-69.2). No toxic deaths occurred. In Arm A, only 4 patients interrupted treatment for toxicity.

Conclusions

Trabectedin is active and well tolerated, retaining similar efficacy across one to three previous lines of chemotherapy.

SUBMITTER: Gadducci A 

PROVIDER: S-EPMC6162262 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature