1406P - Update of the T-DIS randomized phase II trial: Trabectedin rechallenge versus continuation in patients (pts) with advanced soft tissue sarcoma (ASTS)

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Soft Tissue Sarcomas
Presenter Nuria Kotecki
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors N. Kotecki1, A. Le Cesne2, E. Tresch-Bruneel3, O. Mir4, C. Chevreau5, F. Bertucci6, C. Delcambre7, E. Saada-Bouzid8, S. Piperno-Neumann9, J. Bay10, I.L. Ray-Coquard11, T. Ryckewaert1, N. Isambert12, A. Italiano13, S. Clisant14, J. Blay15, N. Penel1
  • 1Medical Oncology, Centre Oscar Lambret, 59020 - Lille/FR
  • 2Medical Oncology, Institut de Cancérologie Gustave Roussy, 94805 - Villejuif/FR
  • 3Clinical Research And Methodological Platform, Centre Oscar Lambret, 59020 - Lille/FR
  • 4Department Of Medical Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 5Oncology, Centre Claudius-Regaud, Toulouse/FR
  • 6Oncologie Médicale, Institute Paoli Calmettes, 13274 - Marseille/FR
  • 7Medicine, Centre Francois Baclesse, Caen/FR
  • 8Medical Oncology, Centre Antoine Lacassagne, Nice/FR
  • 9Medicine, Institut Curie, Paris/FR
  • 10Oncohematology, CHU Estaing, Clermont-Ferrand/FR
  • 11Département D'oncologie Médicale Adulte, Centre Léon Bérard, 69008 - Lyon/FR
  • 12Medicine, Centre Georges-François Leclerc (Dijon), Dijon/FR
  • 13Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 14Clinical Research Unit, Centre Oscar Lambret, 59020 - Lille/FR
  • 15University Claude Bernard Lyon I, Centre Léon Bérard, 69008 - Lyon/FR

Abstract

Background

Trabectedin (T) maintenance beyond 6 cycles (cy) of treatment in responding pts with ASTS is associated with improved progression-free survival (PFS) vs T discontinuation (Le Cesne, Lancet Oncol 2015). The impact of T rechallenge after progressive disease (PD) was prospectively analyzed by the French Sarcoma Group in the national randomized phase II trial (T-DIS; NCT01303094).

Methods

After the initial 6 cy of T (1.5 mg/m2 as 24-h infusion every 3 weeks) pts free of PD were randomly assigned either to continuous treatment with T (C arm; immediate 7th cy) or therapy interruption (I arm). Pts allocated to the I arm could restart T in case of PD (7th cy at the time of PD). Here we report updated outcomes in both arms obtained either from randomization or from the 7th cy date.

Results

From 2/2011 to 3/2013, 178 pretreated pts have been enrolled. Median age and performance status were 57 years (range 19-82) and 1 (range 0-3), respectively. Most pts had leiomyosarcoma (30.0%), liposarcoma (18.0%) or synovial sarcoma (12.0%). 53/178 (29.7%) non progressive patients were eligible for randomization after 6 cy of T, 27 and 26 non progressive pts were randomized to C and I arms, respectively. T has been restarted in 22/26 progressive pts in I arm whereas 25 out of 27 pts of the C arm immediately continued T. Median number of cy after randomization was similar in both arms (5 vs 6 cy, p = 0.96). From the date of randomization the median PFS was 5.3 vs 3.5 months (p = 0.019) in the C and I arm, respectively, and 6-month PFS was 48.2 vs 19.2%. From the date of the 7th cy comparable median PFS (4.2 vs 4.8 months, p = 0.88) and 6-m rates of PFS (45.8% vs 34.7%) were observed in C and I arm, respectively. From the 7th cycle, a favorable trend in longer median OS was observed in C arm (26.0 vs 14.9 months), which did not reach the level of significance (log-rank test p = 0.14) due to the small sample size. Grade ≥3 toxicity rates were not significantly different between the two arms (36.0% vs 38.1%) after T rechallenge (p = 0.88).

Conclusions

Though T remains an active agent at rechallenge, we do not recommend trabectedin discontinuation in pts experiencing stable disease or partial response since interruption of T resulted in a rapid PD in most pts.

Clinical trial identification

EudraCT NCT01303094

Legal entity responsible for the study

Centre Oscar Lambret

Funding

Centre Oscar Lambret

Disclosure

All authors have declared no conflicts of interest.