Journal article
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
Gynecologic oncology, Vol.146(3), pp.531-537
09/2017
DOI: 10.1016/j.ygyno.2017.06.018
PMCID: PMC5783302
PMID: 28651804
Abstract
•Patients with advanced uterine leiomyosarcoma received trabectedin or dacarbazine.•Trabectedin significantly improved progression-free survival vs dacarbazine.•Lack of cumulative toxicity with trabectedin allows for prolonged treatment.
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%).
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.
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.
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.
Details
- Title: Subtitle
- 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
- Creators
- Martee L. Hensley - Memorial Sloan Kettering Cancer CenterShreyaskumar R. Patel - The University of Texas MD Anderson Cancer CenterMargaret von Mehren - Fox Chase Cancer CenterKristen Ganjoo - Stanford Health CareRobin L. Jones - Seattle Cancer Care AllianceArthur Staddon - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteDaniel Rushing - Indiana UniversityMohammed Milhem - University of Iowa Hospitals and ClinicsBradley Monk - St. Joseph's Hospital and Medical CenterGeorge Wang - Janssen (United States)Sharon McCarthy - Janssen (United States)Roland E. Knoblauch - Janssen (United States)Trilok V. Parekh - Janssen (United States)Robert G. Maki - Icahn School of Medicine at Mount SinaiGeorge D. Demetri - Dana-Farber Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Gynecologic oncology, Vol.146(3), pp.531-537
- DOI
- 10.1016/j.ygyno.2017.06.018
- PMID
- 28651804
- PMCID
- PMC5783302
- NLM abbreviation
- Gynecol Oncol
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Publisher
- Elsevier Inc
- Grant note
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (http://dx.doi.org/10.13039/100005984) Janssen Research & Development, LLC P30 CA008748 / MSK Cancer Center Support
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359953802771
Metrics
18 Record Views