Martlee L Hensley (Memorial Sloan Kettering Cancer Center, New York, NY, USA) presented subgroup analysis results of the phase 3 SAR-3007 trial showing that trabectedin improved progression-free survival compared with dacarbazine in women with advanced uterine leiomyosarcoma. 232 women were randomly assigned to either trabectedin (n=144) or dacarbazine (n=88). Median overall survival (the primary endpoint) was 13·4 months in the trabectedin group compared with 12·9 months in the decarbazine group (HR 0·899, 95% CI 0·65–1·24, p=0·5107).
Three-fourths of patients in each group received subsequent anticancer therapy at progression. The subgroup analysis confirmed the significant PFS benefit with trabectedin demonstrated in the overall trial.
The 2.5-month PFS benefit with trabectedin translated into a 43% reduction in the risk of progression (HR, 0.57; 95% CI, 0.41-0.81; P = .0012).
Comparison of all other secondary endpoints demonstrated numerical advantages for the trabectedin arm, including overall response rate (11.2% vs 9.0%), clinical benefit rate (30.6% vs 17.9%), and median duration of response (6.47 vs 4.07 months). Median time to response was similar, 3.22 months with trabectedin and 2.79 months with dacarbazine.
Trabectedin was associated with higher rates of certain adverse events, including elevated liver enzymes (ALT and AST), anemia, neutropenia, leukopenia, and thrombocytopenia. However, rates of grade 3/4 toxicity were generally low in both groups. Dose modifications, including dose reductions and cycle delays, occurred more often with trabectedin.
However, the differences did not translate into less treatment, as 39% of patients in the trabectedin group completed 6 cycles of therapy as compared with 18% of patients in the dacarbazine arm. “The lack of cumulative toxicity with trabectedin allowed for prolonged treatment courses, as more than twice as many patients received at least 6 cycles of therapy,” said Hensley .