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Impact of Trabectedin Interruption and Subsequent Rechallenge on Progression in Patients With Advanced Soft Tissue Sarcoma

Long-term Follow-up of the T-DIS trial

Kotecki, Nuria, MD*; Le Cesne, Axel, MD; Tresch-Bruneel, Emmanuelle, MSc; Ray-Coquard, Isabelle, MD, PhD§; Chevreau, Christine, MD; Bertucci, François, MD, PhD; Bogart, Emilie, MSc; Mir, Olivier, MD, PhD; Pautier, Patricia, MD; Decoupigny, Emilie, MSc#; Clisant, Stéphanie, PharmD#; Blay, Jean-Yves, MD, PhD§; Penel, Nicolas, MD, PhD*

American Journal of Clinical Oncology: November 2018 - Volume 41 - Issue 11 - p 1094–1100
doi: 10.1097/COC.0000000000000430
Original Articles: Soft Tissue

Objective: To assess the impact of trabectedin rechallenge.

Patients and Methods: In the T-DIS trial (NCT0130309), after the 6 initial cycles of trabectedin, patients who were free from progressive disease (PD) were randomly assigned either to continuous treatment with trabectedin (C arm) or therapy interruption (I arm). Patients randomized in the interruption arm were allowed to restart trabectedin in case of PD. Herein we report an update of the impact of trabectedin discontinuation after subsequent rechallenge.

Results: From February 2011 to March 2013, 27 and 26 nonprogressive patients were randomized to C and I arm, respectively. Twenty-two of 26 patients in I arm and 25 of 27 patients in C arm received 7 cycles and more. After randomization, the median number of cycles was similar in both arms (C arm: 5 cycles [range, 1 to 34]; I arm: 6 cycles [range, 1 to 48], P=0.96). After a median follow-up from randomization of 35.3 months, continuous treatment with trabectedin was associated with a significant improvement in progression-free survival compared with the rechallenge arm (5.3 vs. 3.5 mo, P=0.019). The observed difference in median overall survival from the seventh cycle did not meet the level of significance (26.0 vs. 14.9 mo, P=0.14). The safety profile was similar in both arms. Mean time spent without symptoms and toxicity (Q-TWIST) was higher in the C arm, but the difference did not reach the level of significance.

Conclusions: We have demonstrated that trabectedin retains its activity when patients are rechallenged on progression after a treatment break.

*Medical Oncology Department

Methodology and Biostatistics Unit

#Clinical Research Unit, Centre Oscar Lambret

Medical Oncology, Institut Claudius Regaud, Cedex

Medical Oncology Department, Villejuif

§Medical Oncology Department, Centre Léon Bérard, Lyon

Medical Oncology Department, Institut Paoli Calmette, Marseille, France

Supported through a competitive national research (PHRC) grant from the National Cancer Institute of France (INCa) ( PharmaMar, S.A. had supplied drug for the randomized part of the trial. PharmaMar, S.A. had no role in study design, collection, analysis, or interpretation of data. The corresponding author had full access to all of the data and the final responsibility to submit for publication.

The authors declare no conflicts of interest.

Reprints: Nicolas Penel, MD, PhD, Department of General Oncology, Centre Oscar Lambret, 3, rue F Combemale, 59020 Lille, France. E-mail:

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.