Hensley, M. L., Patel, S. R., von Mehren, M., Ganjoo, K., Jones, R. L., Staddon, A., Rushing, D., Milhem, M., Monk, B., Wang, G., McCarthy, S., Knoblauch, R. E., Parekh, T. V., Maki, R. G., Demetri, G. D. (September 2017) Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol, 146 (3). pp. 531-537. ISSN 0090-8258
Abstract
OBJECTIVE: Trabectedin demonstrated significantly improved disease control in leiomyosarcoma and liposarcoma patients in a global phase 3 trial (NCT01343277). A post hoc analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in women with uterine leiomyosarcoma (uLMS), the largest subgroup of enrolled patients (40%). METHODS: Of 577 patients randomized 2:1 to receive trabectedin 1.5mg/m2 by 24-hour IV infusion or dacarbazine 1g/m2 by 20-120-minute IV infusion once every three weeks, 232 had uLMS (trabectedin: 144; dacarbazine: 88). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR: complete responses+partial responses+stable disease [SD] for at least 18weeks), duration of response (DOR), and safety. RESULTS: PFS for trabectedin was 4.0months compared with 1.5months for dacarbazine (hazard ratio [HR]=0.57; 95% CI 0.41-0.81; P=0.0012). OS was similar (trabectedin 13.4months vs. dacarbazine 12.9months, HR=0.89; 95% CI 0.65-1.24; P=0.51) between groups. ORR was 11% with trabectedin vs. 9% with dacarbazine (P=0.82). CBR for trabectedin was 31% vs. 18% with dacarbazine (P=0.05); median DOR was 6.5months for trabectedin vs. 4.1months for dacarbazine (P=0.32). Grade 3/4 treatment-emergent adverse events observed in >/=10% of patients in the trabectedin group included transient aminotransferase (aspartate/alanine) elevations, anemia, leukopenia, and thrombocytopenia. CONCLUSIONS: In this post hoc subset analysis of patients with uLMS who had received prior anthracycline therapy, trabectedin treatment resulted in significantly longer PFS versus dacarbazine, with an acceptable safety profile. There was no difference in OS.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Dacarbazine Phase 3 Trabectedin Uterine leiomyosarcoma |
| Subjects: | diseases & disorders > cancer diseases & disorders > cancer > drugs and therapies |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Signal Transduction CSHL labs > Maki lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program |
| Depositing User: | Matt Covey |
| Date: | September 2017 |
| Date Deposited: | 21 Jul 2017 15:48 |
| Last Modified: | 06 Jul 2021 19:27 |
| PMCID: | PMC5783302 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/35058 |
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