Jones RL1, Demetri GD2, Schuetze SM3, Milhem M4, Elias A5, Van Tine BA6, Hamm J7, McCarthy S8, Wang G9, Parekh T8, Knoblauch R8, Hensley ML10, Maki RG11, Patel S12, von Mehren M13
Author :
1.- Seattle Cancer Care Alliance, Seattle, USA; currently at Royal Marsden Hospital/Institute of Cancer Research, London, UK.
2.- Center for Sarcoma and Bone Oncology, Dana Farber Cancer Institute; Ludwig Center at Harvard; Boston, USA.
3.- University of Michigan Health System, Ann Arbor, USA.
4.- University of Iowa Hospitals and Clinics, Iowa City, USA.
5.- University of Colorado Cancer Center, Aurora, USA.
6.- Division of Oncology, Washington University in St. Louis, St. Louis, USA.
7.- Norton Cancer Institute, Louisville, USA.
8.- Clinical Oncology, Janssen Research and Development, Raritan, USA.
9.- Clinical Biostatistics, Janssen Research and Development, Raritan, USA.
10.- Memorial Sloan Kettering Cancer Center, New York, USA.
11.- Monter Cancer Center, Northwell Health, Lake Success, USA, and Cold Spring Harbor Laboratory, Cold Spring Harbor, USA.
12.- Department of Sarcoma Medical Oncology, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, USA.
13.- Department of Hematology and Medical Oncology, Fox Chase Cancer Center, Philadelphia, USA.
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.