A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial.
randomized trial
soft tissue sarcoma
trabectedin
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
16
02
2021
revised:
20
04
2021
accepted:
22
04
2021
pubmed:
2
5
2021
medline:
14
8
2021
entrez:
1
5
2021
Statut:
ppublish
Résumé
The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS). This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin. Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.
Sections du résumé
BACKGROUND
The French Sarcoma Group assessed the efficacy, safety, and quality of life (QoL) of trabectedin versus best supportive care (BSC) in patients with advanced soft tissue sarcoma (STS).
PATIENTS AND METHODS
This randomized, multicenter, open-label, phase III study included adults with STS who progressed after 1-3 prior treatment lines. Patients were randomized (1 : 1) to receive trabectedin 1.5 mg/m
RESULTS
Between 26 January 2015 and 5 November 2015, 103 heavily pre-treated patients (60.2% with L-STS) from 16 French centers were allocated to receive trabectedin (n = 52) or BSC (n = 51). Median PFS was 3.1 months [95% confidence interval (CI) 1.8-5.9 months] in the trabectedin arm versus 1.5 months (0.9-2.6 months) in the BSC arm (hazard ratio = 0.39, 95% CI 0.24-0.64, P < 0.001) with benefits observed across almost all analyzed subgroups, but particularly in patients with L-STS (5.1 versus 1.4 months, P = 0.0001). Seven patients (13.7%) in the trabectedin arm (all with L-STS) achieved a partial response, while no objective responses were observed in the BSC arm (P = 0.004). The most common grade 3/4 adverse events were neutropenia (44.2% of patients), leukopenia (34.6%), and transaminase increase (32.7%). Health-related 30-item core European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire evidenced no statistical differences between the arms for any domain and at any time point. After progression, 91.8% of patients crossed over from BSC to trabectedin.
CONCLUSION
Trabectedin demonstrates superior disease control to BSC without impairing QoL in patients with recurrent STS of multiple histologies, with greater impact in patients with L-STS.
Identifiants
pubmed: 33932507
pii: S0923-7534(21)01171-6
doi: 10.1016/j.annonc.2021.04.014
pii:
doi:
Substances chimiques
Antineoplastic Agents, Alkylating
0
Dioxoles
0
Tetrahydroisoquinolines
0
Trabectedin
ID0YZQ2TCP
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1034-1044Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure ALC has received honoraria from Deciphera, Bayer, and PharmaMar. J-YB has received research support and honoraria from PharmaMar, Bayer, and Eisai. IR-C reports research support and honoraria from PharmaMar, Roche, AstraZeneca, Clovis, GSK, Mersana, Deciphera, Genentech, Advaxis, MSD, and BMS. OM has served as consultant for Amgen, AstraZeneca, Bayer, Bristol Myers-Squibb, Eli-Lilly, Ipsen, Lundbeck, MSD, Novartis, Pfizer, Roche, Servier, and Vifor Pharma, and is a shareholder of Amplitude surgical, Ipsen, and Transgene. All other authors have declared no conflicts of interest. Data sharing De-identified individual data might be made available following publication by reasonable request and on a case-by-case basis to the corresponding author, including the clinical study results and statistical analysis plan. A research proposal should be included, which will be evaluated by the French Sarcoma Group and the ethics committee for clinical investigation.