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.
Original languageItalian
Pages (from-to)565-571
Number of pages7
JournalBritish Journal of Cancer
Volume119
Issue number5
DOIs
Publication statusPublished - Aug 2018

Cite this

@article{c82c41ed203c48d990baedf69d3c7b63,
title = "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.",
author = "Angiolo Gadducci and Federica Grosso and Giovanni Scambia and Francesco Raspagliesi and Nicoletta Colombo and Giovanni Grignani and Paolo Casali and Roberta Sanfilippo and Angela Buonadonna and Armando Santoro and Milena Bruzzone and Grazia Artioli and Domenica Lorusso and Elena Biagioli and Roldano Fossati and Francesca Galli and Emanuele Negri and Eliana Rulli and Valter Torri and Maurizio D'Incalci",
year = "2018",
month = "8",
doi = "10.1038/s41416-018-0190-y",
language = "Italian",
volume = "119",
pages = "565--571",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - A phase II randomised (calibrated design) study on the activity of the single-agent trabectedin in metastatic or locally relapsed uterine leiomyosarcoma

AU - Gadducci, Angiolo

AU - Grosso, Federica

AU - Scambia, Giovanni

AU - Raspagliesi, Francesco

AU - Colombo, Nicoletta

AU - Grignani, Giovanni

AU - Casali, Paolo

AU - Sanfilippo, Roberta

AU - Buonadonna, Angela

AU - Santoro, Armando

AU - Bruzzone, Milena

AU - Artioli, Grazia

AU - Lorusso, Domenica

AU - Biagioli, Elena

AU - Fossati, Roldano

AU - Galli, Francesca

AU - Negri, Emanuele

AU - Rulli, Eliana

AU - Torri, Valter

AU - D'Incalci, Maurizio

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

U2 - 10.1038/s41416-018-0190-y

DO - 10.1038/s41416-018-0190-y

M3 - Articolo

VL - 119

SP - 565

EP - 571

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 5

ER -