Trabectedin-olaparib combination or trabectedin in advanced soft tissue sarcomas after failure of anthracycline-based treatment (TOMAS2)
Investigators treated patients with advanced/metastatic soft tissue sarcomas (STS) who had progressed on a kind of chemotherapy called anthracycline based regimens with a combination of trabectedin (a different chemotherapy) and olaparib, which inhibits a protein called PARP (which helps repair DNA and the inhibition of which can cause tumor cells to die), or trabectedin alone. In all, 130 patients were enrolled in this phase 2 clinical trial. With a median follow-up of 37.4 months, the 6-month progression-free survival (PFS) was 32% for trabectedin and olaparib vs. 28% for trabectedin alone. The median PFS Was 3.9 months with trabectedin and olaparib vs. 2.9 months with trabectedin alone. The overall response rate was 12.7% vs. 7.9%, respectively. Notably, in patients with uterine leiomyosarcoma, the 12-month PFS was 42.9% with trabectedin and olaparib vs. 0% with trabectedin alone. The investigators also tested for PARP expression and found that it significantly correlated with improved PFS with trabectedin-olaparib. Although more research is needed, these results indicate that uterine leiomyosarcoma may be a good candidate for chemotherapy plus PARP inhibitor combination therapy and that PARP expression may be a biomarker to identify patients more likely to respond.
Read the full study in Annals of Oncology.