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).
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.
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).
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.
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Centre Oscar Lambret
Centre Oscar Lambret
All authors have declared no conflicts of interest.