CHICAGO – Trabectedin (Yondelis) was superior to best supportive care at prolonging progression-free survival in patients with heavily pretreated advanced leiomyosarcomas and liposarcomas, investigators in the randomized phase 3 T-SAR trial reported.
Among 103 patients with soft-tissue sarcomas that had progressed after two to four lines of standard chemotherapy, median progression-free survival (PFS) for patients randomized to trabectedin was 3.12 months, compared with 1.51 for patients randomized to best supportive care.
This difference translated into a hazard ratio (HR) favoring trabectedin of 0.39 (P less than .0001), Axel Le Cesne, MD, of Gustave Roussy Cancer Institute in Villejuif, France, reported on behalf of colleagues in the French Sarcoma Group.
All of the benefit was apparently among patients with what he termed “L-sarcomas” – leiomyosarcoma and liposarcoma – compared with other sarcoma histologies.
“The tumor control rate after six courses of trabectedin is similar to previous studies. As already reported, trabectedin is well-tolerated,” he said at the annual meeting of the American Society of Clinical Oncology.
Trabectedin was shown to be superior to best supportive care at delaying disease progression among patients with advanced translocation-related sarcomas in a randomized phase 2 trial in Japan, but had not been studied in this setting against other sarcoma histologies, Dr. Le Cesne said.
The investigators enrolled 103 patients and randomly assigned them to receive either best supportive care or trabectedin in a 1.5 mg/m2 infusion over 24 hours every 3 weeks. Patients in the best supportive care arm could be crossed over to the trabectedin arm at the time of progression.
Sarcoma histologies included liposarcoma, leiomyosarcoma, undifferentiated sarcomas, myxofibrosarcoma, synovial sarcoma, and others. The L-sarcomas accounted for 60.2% of the patient population.
Fifty-two patients were randomized to trabectedin and 51 to best supportive care, but 2 patients assigned to best supportive care dropped out soon after randomization, leaving 52 and 49 patients, respectively, for the as-treated analysis. All 103 patients were assessable for efficacy.
After a median follow-up of 26 months, median PFS for all patients, as noted before, was 3.12 months in the trabectedin arm and 1.51 months in the best supportive care arm.
The overall response rate in the trabectedin arm was 13.7%, composed of seven partial responses. There were no responses in the best supportive care arm. In all, 66.7% of patients in the trabectedin arm and 61.2% of patients in the best supportive care arm had stable disease, and 19.6% and 38.8%, respectively, had disease progression.
An analysis of PFS by sarcoma histology showed that all of the benefit appeared to be in patients with L-sarcomas, with a median PFS for trabectedin-treated patients of 5.13 months compared with 1.41 months for controls (HR 0.29, P less than .0001).
In contrast, there was no significant difference between the groups among patients with non–L sarcomas, with respective median PFS of 1.81 and 1.51 months (HR 0.60, P = .16). There were no treatment responses among patients in either treatment arm in this subgroup.
Not surprisingly, there were more grade 3 or 4 adverse events among patients in the trabectedin arm. Neutropenia was seen in 23 patients given trabectedin and 1 given best supportive care; leukopenia in 18 patients vs. 0, thrombocytopenia in 13 vs. 0, and elevated liver transaminases in 17 vs. 1, respectively.
In all, 45 of the 49 patients who were treated in the best supportive care arm were crossed over to trabectedin.
Median overall survival was 13.6 months in the trabectedin arm and 10.8 months in the best supportive care arm. This difference was not statistically significant.
Dr Le Cesne noted that the tumor control rate of 30% with trabectedin was similar to that seen in an earlier French trial (Lancet Oncol. 2015 Mar 1;16[3]:312-19).
Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
SOURCE: Le Cesne A et al. ASCO 2018. Abstract 11508.