Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas

Jean Yves Blay, Michael G. Leahy, Binh Bui Nguyen, Shreyaskumar R. Patel, Peter Hohenberger, Armando Santoro, Arthur P. Staddon, Nicolas Penel, Sophie Piperno-Neumann, Andrew Hendifar, Pilar Lardelli, Antonio Nieto, Vicente Alfaro, Sant P. Chawla

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5 mg/m2 24-h intravenous (i.v.) infusion every 3 weeks (q3wk) (Arm A), or doxorubicin 75 mg/m2 i.v. q3wk, or doxorubicin 60 mg/m2 i.v. plus ifosfamide (range, 6-9 g/m2) i.v. q3wk (Arm B). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p = 0.9573; hazard ratio = 0.86, p = 0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.

Original languageEnglish
Pages (from-to)1137-1147
Number of pages11
JournalEuropean Journal of Cancer
Volume50
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

trabectedin
Sarcoma
Doxorubicin
Drug Therapy
Disease-Free Survival
Therapeutics
Ifosfamide
Mucositis
Alopecia
Neutropenia
Intravenous Infusions

Keywords

  • Chemotherapy
  • Sarcomas
  • Trabectedin
  • Translocation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. / Blay, Jean Yves; Leahy, Michael G.; Nguyen, Binh Bui; Patel, Shreyaskumar R.; Hohenberger, Peter; Santoro, Armando; Staddon, Arthur P.; Penel, Nicolas; Piperno-Neumann, Sophie; Hendifar, Andrew; Lardelli, Pilar; Nieto, Antonio; Alfaro, Vicente; Chawla, Sant P.

In: European Journal of Cancer, Vol. 50, No. 6, 2014, p. 1137-1147.

Research output: Contribution to journalArticle

Blay, JY, Leahy, MG, Nguyen, BB, Patel, SR, Hohenberger, P, Santoro, A, Staddon, AP, Penel, N, Piperno-Neumann, S, Hendifar, A, Lardelli, P, Nieto, A, Alfaro, V & Chawla, SP 2014, 'Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas', European Journal of Cancer, vol. 50, no. 6, pp. 1137-1147. https://doi.org/10.1016/j.ejca.2014.01.012
Blay, Jean Yves ; Leahy, Michael G. ; Nguyen, Binh Bui ; Patel, Shreyaskumar R. ; Hohenberger, Peter ; Santoro, Armando ; Staddon, Arthur P. ; Penel, Nicolas ; Piperno-Neumann, Sophie ; Hendifar, Andrew ; Lardelli, Pilar ; Nieto, Antonio ; Alfaro, Vicente ; Chawla, Sant P. / Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. In: European Journal of Cancer. 2014 ; Vol. 50, No. 6. pp. 1137-1147.
@article{efdbdee6370f402085f4983b8a262880,
title = "Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas",
abstract = "This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5 mg/m2 24-h intravenous (i.v.) infusion every 3 weeks (q3wk) (Arm A), or doxorubicin 75 mg/m2 i.v. q3wk, or doxorubicin 60 mg/m2 i.v. plus ifosfamide (range, 6-9 g/m2) i.v. q3wk (Arm B). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p = 0.9573; hazard ratio = 0.86, p = 0.6992). At the time of this analysis, 63.9{\%} and 58.3{\%} of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0{\%} versus 5.9{\%}), but response according to Choi criteria showed fewer differences between treatment arms (45.9{\%} versus 37.3{\%}). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.",
keywords = "Chemotherapy, Sarcomas, Trabectedin, Translocation",
author = "Blay, {Jean Yves} and Leahy, {Michael G.} and Nguyen, {Binh Bui} and Patel, {Shreyaskumar R.} and Peter Hohenberger and Armando Santoro and Staddon, {Arthur P.} and Nicolas Penel and Sophie Piperno-Neumann and Andrew Hendifar and Pilar Lardelli and Antonio Nieto and Vicente Alfaro and Chawla, {Sant P.}",
year = "2014",
doi = "10.1016/j.ejca.2014.01.012",
language = "English",
volume = "50",
pages = "1137--1147",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",
number = "6",

}

TY - JOUR

T1 - Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas

AU - Blay, Jean Yves

AU - Leahy, Michael G.

AU - Nguyen, Binh Bui

AU - Patel, Shreyaskumar R.

AU - Hohenberger, Peter

AU - Santoro, Armando

AU - Staddon, Arthur P.

AU - Penel, Nicolas

AU - Piperno-Neumann, Sophie

AU - Hendifar, Andrew

AU - Lardelli, Pilar

AU - Nieto, Antonio

AU - Alfaro, Vicente

AU - Chawla, Sant P.

PY - 2014

Y1 - 2014

N2 - This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5 mg/m2 24-h intravenous (i.v.) infusion every 3 weeks (q3wk) (Arm A), or doxorubicin 75 mg/m2 i.v. q3wk, or doxorubicin 60 mg/m2 i.v. plus ifosfamide (range, 6-9 g/m2) i.v. q3wk (Arm B). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p = 0.9573; hazard ratio = 0.86, p = 0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.

AB - This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5 mg/m2 24-h intravenous (i.v.) infusion every 3 weeks (q3wk) (Arm A), or doxorubicin 75 mg/m2 i.v. q3wk, or doxorubicin 60 mg/m2 i.v. plus ifosfamide (range, 6-9 g/m2) i.v. q3wk (Arm B). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p = 0.9573; hazard ratio = 0.86, p = 0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma.

KW - Chemotherapy

KW - Sarcomas

KW - Trabectedin

KW - Translocation

UR - http://www.scopus.com/inward/record.url?scp=84897074467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897074467&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2014.01.012

DO - 10.1016/j.ejca.2014.01.012

M3 - Article

C2 - 24512981

AN - SCOPUS:84897074467

VL - 50

SP - 1137

EP - 1147

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 6

ER -