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. Eligible patients had received ≥ one line of chemotherapy. Gemcitabine ± docetaxel naive patients were randomised to Arm A: trabectedin 1.3 mg/m or calibration Arm B: gemcitabine 900 mg/m and docetaxel 75 mg/m . 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%. 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. Trabectedin is active and well tolerated, retaining similar efficacy across one to three previous lines of chemotherapy.
Gadducci, A., Grosso, F., Scambia, G., Raspagliesi, F., Colombo, N., Grignani, G.
, ... D'Incalci, M. (2018). A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma. British Journal of Cancer
, 565-571. https://doi.org/10.1038/s41416-018-0190-y