Efficacy and tolerability of trabectedin in elderly patients with sarcoma: subgroup analysis from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma

Jones, R. L., Demetri, G. D., Schuetze, S. M., Milhem, M., Elias, A., Van Tine, B. A., Hamm, J., McCarthy, S., Wang, G., Parekh, T., Knoblauch, R., Hensley, M. L., Maki, R. G., Patel, S., von Mehren, M. (August 2018) Efficacy and tolerability of trabectedin in elderly patients with sarcoma: subgroup analysis from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma. Ann Oncol. ISSN 0923-7534

URL: https://www.ncbi.nlm.nih.gov/pubmed/30084934
DOI: 10.1093/annonc/mdy253

Abstract

Background: Treatment options for soft tissue sarcoma patients aged >/=65 years (elderly) can be limited by concerns regarding the increased risk of toxicity associated with standard systemic therapies. Trabectedin has demonstrated improved disease control in a phase 3 trial (ET743-SAR-3007) of patients with advanced liposarcoma or leiomyosarcoma (LPS/LMS) after failure of anthracycline-based chemotherapy. Since previous retrospective analyses have suggested that trabectedin has similar safety and efficacy outcomes regardless of patient age, we performed a subgroup analysis of the safety and efficacy observed in elderly patients enrolled in this trial. Patients and Methods: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every-3-weeks. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), time-to-progression, objective response rate (ORR), duration of response, symptom severity, and safety. A post hoc analysis was conducted in the elderly patient subgroup. Results: Among 131 (trabectedin=94; dacarbazine=37) elderly patients, disease characteristics were well-balanced and consistent with those of the total study population. Treatment exposure was longer in patients treated with trabectedin versus dacarbazine (median 4 versus 2 cycles, respectively), with a significantly higher proportion receiving prolonged therapy (>/=6 cycles) in the trabectedin arm (43% versus 23%, respectively; p=0.04). Elderly patients treated with trabectedin showed significantly improved PFS (4.9 versus 1.5 months, respectively; hazard ratio [HR]=0.40; p=0.0002) but no statistically significant improvement in OS (15.1 versus 8.0 months, respectively; HR = 0.72; p=0.18) or ORR (9% versus 3%, respectively; p=0.43). The safety profile for elderly trabectedin-treated patients was comparable to that of the overall trabectedin-treated study population. Conclusions: This subgroup analysis of the elderly population of ET743-SAR-3007 suggests that elderly patients with soft tissue sarcoma and good performance status can expect clinical benefit from trabectedin similar to that observed in younger patients. Trial registration: www.clinicaltrials.gov, NCT01343277.

Item Type: Paper
Subjects: diseases & disorders > cancer > drugs and therapies > chemotherapy
diseases & disorders > cancer > cancer types > sarcoma
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matthew Dunn
Date: 2 August 2018
Date Deposited: 14 Aug 2018 15:51
Last Modified: 14 Aug 2018 15:51
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37119

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