Neoadjuvant Trabectedin Noninferior to Standard Care for High-Grade Myxoid Liposarcoma

Neoadjuvant trabectedin may be an alternative to standard chemotherapy for patients with high-grade myxoid liposarcoma of the extremities or trunk, according to researchers.¹

They found that trabectedin was noninferior to standard neoadjuvant treatment with an anthracycline and ifosfamide in a phase 3 trial. The results were published in the Journal of Clinical Oncology.

The trial (ClinicalTrials.gov Identifier: NCT01710176) was designed to compare standard neoadjuvant therapy to a histology-tailored regimen in patients with localized high-risk soft tissue sarcoma.

Prior results from the trial suggested that standard therapy was superior to histology-tailored treatment for all histologies except high-grade myxoid liposarcoma.² For these patients, standard and tailored therapy appeared equivalent.

To compare the treatments further, researchers evaluated 101 patients with high-grade myxoid liposarcoma of the extremities or trunk.¹ The patients were randomly assigned to receive neoadjuvant histology-tailored treatment with trabectedin (n=45) or standard neoadjuvant treatment with an anthracycline and ifosfamide (n=56).

At a median follow-up of 66 months, there were 15 recurrences in the standard therapy arm (3 local, 11 distant, and 1 local-distant) and 7 recurrences in the trabectedin arm (6 distant and 1 local-distant).

The disease-free survival (DFS) probabilities at 60 months were 0.73 (95% CI, 0.58-0.83) in the standard arm and 0.86 (95% CI, 0.68-0.94) in the trabectedin arm. Trabectedin was noninferior to standard therapy for DFS (hazard ratio [HR], 0.60; 95% CI, 0.24-1.46; P =.26).

There were 6 deaths in the standard treatment arm and 5 deaths in the trabectedin arm. The overall survival (OS) probabilities at 60 months were 0.90 (95% CI, 0.74-0.96) in the standard arm and 0.88 (95% CI, 0.70-0.95) in the trabectedin arm. Trabectedin was noninferior to standard therapy for OS (HR, 1.20; 95% CI, 0.37-3.93; P =.77).

Eighty-two patients were evaluable for response. There were 3 responses (6.5%) in the standard arm and 4 responses (11.1%) in the trabectedin arm. All were partial responses.

Of the remaining patients, 38 (82.6%) in the standard arm and 36 (88.9%) in the trabectedin arm had stable disease. Progression was observed in 3 patients (6.5%) in the standard arm and none of the patients in the trabectedin arm.

There were no treatment-related deaths. Major grade 3-4 toxicities (in the standard and trabectedin arms, respectively) included neutropenia (67% vs 7%), febrile neutropenia (24% vs 0%), thrombocytopenia (20% vs 0%), anemia (15% vs 0%), ALT/AST increase (4% vs 7%), and nausea and vomiting (4% vs 2%).

The researchers noted that the main limitation of this study is that it included patients with a limited risk of recurrence.

“It is not possible to rule out that the lack of difference between the two chemotherapy regimens might simply be the result of a lack of effect of the neoadjuvant therapy as such, rather than an equivalence of the therapeutic effect,” the researchers wrote. “Additionally, the number of randomized patients and the number of events are small for a noninferiority study.”

Still, the researchers concluded that the outcomes with the 2 regimens “were clearly comparable,” so trabectedin could be an alternative to standard neoadjuvant therapy for patients with high-grade myxoid liposarcoma of the extremities or trunk.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor