A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: the TRUSTS trial.
OBJECTIVE
To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour infusion) in terms of safety, convenience and efficacy.


METHODS
In this randomised multicentre prospective dose-selection phase IIb superiority trial, 133 patients were randomised between doxorubicin (n=43), trabectedin (3-hour infusion, T3h) (n=47) and trabectedin (24-hour infusion, T24h) (n=43). PFS was defined as time from random assignment until objective progression by response evaluation criteria in solid tumours (RECIST 1.1), a global deterioration of the health status requiring discontinuation of the treatment, or death from any cause.


RESULTS
The study was terminated due to lack of superiority in both trabectedin treatment arms as compared to the doxorubicin control arm. Median PFS was 2.8months in the T3h arm, 3.1months in the T24h arm and 5.5months in the doxorubicin arm. No significant improvements in PFS were observed in the trabectedin arms as compared to the doxorubicin arm (T24h versus doxorubicin: hazard ratio (HR) 1.13, 95% confidence interval (CI) 0.67-1.90, P=.675; T3h versus doxorubicin: HR 1.50, 95% CI 0.91-2.48, P=.944). Only one toxic death occurred in the T3h arm, but treatment had to be stopped due to toxicity in 7 (15.2%) (T3h), 8 (19.5%) (T24h) and 1 (2.5%) doxorubicin patients.


CONCLUSIONS
Doxorubicin continues to be the standard treatment in eligible patients with advanced/metastatic soft-tissue sarcoma (STS). Trabectedin 1.5mg/m(2)/24-hour infusion is the overall proven approach to delivering this agent in the second-line setting for patients with advanced or metastatic STS.
Department of Medical Oncology, Institut Bergonié, Comprehensive Cancer Centre, F-33076 Bordeaux, France. Electronic address: b.bui@bordeaux.unicancer.fr.
B
B
Bui-Nguyen
Dana-Farber Cancer Institute, Boston, USA.
J E
JE
Butrynski
Centre Oscar Lambret, 59020 Lille Cedex, France.
N
N
Penel
Université Claude Bernard & Centre Léon Bérard, Lyon, France.
J Y
JY
Blay
Centre G-F Leclerc, 1 rue du Pr Marion, 21079 Dijon Cedex, France.
N
N
Isambert
University of Iowa Hospital and Clinics, Iowa City, USA.
M
M
Milhem
The Netherlands Cancer Institute (NKI) - Antoni van Leeuwenhoekziekenhuis, Amsterdam, The Netherlands.
J M
JM
Kerst
University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
A K L
AK
Reyners
EORTC Headquarters, Brussels, Belgium.
S
S
Litière
EORTC Headquarters, Brussels, Belgium.
S
S
Marréaud
Centre G-F Leclerc, 1 rue du Pr Marion, 21079 Dijon Cedex, France.
F
F
Collin
Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
W T A
WT
van der Graaf
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D004149:Dioxoles / Q000008:administration & dosage*; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy*; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage*; D000077606:Trabectedin
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D004317:Doxorubicin; D000077606:Trabectedin
Clinical trial; Doxorubicin; First line chemotherapy; Metastatic; Soft-tissue sarcoma; Trabectedin