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

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