1414O - Benefit of maintenance therapy with trabectedin (T) beyond the 6 first cycles: Results of a prospective randomized phase II trial comparing interru...

Date 29 September 2014
Event ESMO 2014
Session Sarcoma
Topics Anticancer Agents
Soft Tissue Sarcomas
Biological Therapy
Presenter Axel Le Cesne
Citation Annals of Oncology (2014) 25 (suppl_4): iv494-iv510. 10.1093/annonc/mdu354
Authors A. Le Cesne1, J. Blay2, T. Ryckewaert3, C. Chevreau4, F. Bertucci5, C. Delcambre6, E. Saada7, S. Piperno-Neumann8, J. Bay9, O. Mir10, J. Domont11, I.L. Ray-Coquard12, T. Valentin4, E. Tresch13, S. Clisant14, N. Isambert15, A. Italiano16, N. Badri17, N. Penel3
  • 1Medical Oncology, Institut Gustave Roussy, FR-94805 - Villejuif CEDEX/FR
  • 2Oncology, Centre Léon Bérard, 69008 - Lyon/FR
  • 3Medical Oncology, Centre Oscar Lambret, 59000 - Lille/FR
  • 4Medical Oncology, Institut Claudius Régaud, 31052 - Toulouse/FR
  • 5Medical Oncology, Institut Paoli Calmette, Marseille/FR
  • 6Hôpital De Jour, Centre Francois Baclesse, Caen/FR
  • 7Medical Oncology, institut Lacassagne, nice/FR
  • 8Medical Oncology, Institut Curie, 75248 - Paris/FR
  • 9Service De Médecine, Centre Hospitalier Universitaire, Clermont-Ferrand/FR
  • 10Medecine, Institut Gustave Roussy, FR-94805 - Villejuif CEDEX/FR
  • 11Dept. Medical Oncology, Institut Gustave Roussy, 94805 - VILLEJUIF/FR
  • 12Medical Oncology, Centre Léon Bérard, 69008 - Lyon CEDEX/FR
  • 13Biostatistics Unit, Centre Oscar Lambret, 59000 - Lille/FR
  • 14Clinical Research, Centre Oscar Lambret, 59000 - Lille/FR
  • 15Medical Oncology, Centre Georges François Leclerc, 21000 - Dijon/FR
  • 16Medical Oncology, Institute Bergonie, FR-33076 - Bordeaux CEDEX/FR
  • 17Medical Oncology, Pharmamar, Madrid/ES



Retrospective data suggest that T maintenance beyond 6 cycles (cy) of treatment in responding pts with ASTS is associated with better outcome. We report here the result of a randomized phase II trial investigating clinical benefit of continuation of treatment until progression vs. drug-holiday (T-Dis trial; EudraCT 2010-022613-26).


After the initial 6 cy of T (1.5 mg/m2 as 24-h infusion every 3 weeks), pts free from progressive disease (PD) were randomly assigned either to continuous treatment with T (C arm) or therapy interruption (I arm). Pts who declined randomization could continue with T. Pts allocated to the I arm could restart T in case of PD. Primary endpoint was PFS rate at 6 months (m) after randomization.


From February 2011 to March 2013, 178 pretreated pts have been enrolled. At inclusion, the pts had a median age of 57.5 years (range 19-82) and a median performance status of 1 (range 0-3) and most had leiomyo- (30%), lipo- (18%) or synovial sarcoma (12%). Among evaluable pts (n=178), the rate of non-progression after the initial 6 cycles of T was higher than expected (n=53; 29.7%). After 6 cy of T, 27 and 26 non progressive pts were randomized to C and I arm, respectively, and received a similar median number of T cy: 5 (range 2-17) for C arm and 5 (range 1-12) for I arm. In May 2014, the median PFS after randomization was 7.2 m in C and 4.0 m in I arm (p=0.031), the 6-m PFS of 51.9% (31.9-68.6) and 23.1% (9.4-40.3) for C and I arm. The 12-m OS rate after randomization was 84.6% (63.9-93.9) and 69.2% (43.3-85.0) for C and I arm, respectively. T has been reintroduced in 21/26 pts who progressed in I arm (PFS at re-challenge: 3.8 months). Occurrence of grade 3 (16.0 vs. 14.3%), grade 4 (4.0 vs. 0.0%) related toxicities and SAEs (0 vs. 0%) were similar in both arms.


The rate of non-progression after 6 cy of T was higher than previously reported, probably due to a better selection of ASTS pts in referral centers and a better management of T. Continuation of T beyond the 6th cy until progression was associated with statistically significant improvement of PFS. Analysis of impact on OS requires longer follow-up.


A. Le Cesne: Research Grant from Pharmamar; J. Blay: Research Grant from Pharmamar A. Italiano: Research Grant from Pharmamar; N. Badri: Employed by Pharmamar; N. Penel: Research Grant from Pharmamar. All other authors have declared no conflicts of interest.