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 Anti-Cancer Agents & Biologic Therapy
Soft Tissue Sarcomas
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.