Effectiveness and Safety of Trabectedin and Radiotherapy for Patients With Myxoid Liposarcoma: A Nonrandomized Clinical Trial.

Importance: Preclinical data about the synergistic activity of radiotherapy (RT) and trabectedin have been reported. The combination of trabectedin and RT in treating myxoid liposarcomas appears worth exploring. Objective: To explore the effectiveness and safety of trabectedin combined with RT. Design, Setting, and Participants: This international, open-label, phase 2 nonrandomized clinical trial including 46 patients with myxoid liposarcoma was conducted in 4 centers in Spain, 1 in Italy, and 2 in France from July 1, 2016, to September 30, 2019. Eligible patients had to have a histologic, centrally reviewed diagnosis of localized resectable myxoid liposarcoma arising from an extremity or the trunk wall. Interventions: Trabectedin was administered at the recommended dose stemming from the phase 1 trial (1.5 mg/m2), with intravenous infusion during 24 hours every 21 days for a total of 3 cycles. Radiotherapy was started after completion of the first trabectedin infusion (cycle 1, day 2). Patients received 25 fractions of radiation for a total of 45 Gy. Surgery was planned 3 to 4 weeks after the administration of the last preoperative cycle and not until 4 weeks after the end of preoperative RT. Pathologic specimens were mapped in tumor sections to estimate the histologic changes and the percentage of viable tumor after neoadjuvant treatment. Main Outcomes and Measures: The primary objective of the phase 2 part of the study was overall response. Secondary objectives were effectiveness measured by relapse-free survival and activity measured by functional imaging and pathologic response. Results: A total of 46 patients were enrolled. Four patients were not evaluable. The median age was 43 years (range, 18-77 years), and 31 patients were male (67%). Overall, 9 of 41 patients (22%) achieved a partial response with neoadjuvant treatment with trabectedin and RT, with 5 of 39 patients (13%) achieving a complete pathologic response and 20 of 39 patients (51%) having 10% or less of a viable remaining tumor. Partial responses according to Choi criteria were observed in 24 of 29 evaluable patients (83%), and no patient had disease progression. Treatment was well tolerated. Conclusions and Relevance: Although the primary end point of this phase 2 nonrandomized clinical trial was not met (Response Evaluation Criteria in Solid Tumors response in ≥70% of patients), results suggest this combination was well tolerated and effective in terms of pathologic response. Thus, trabectedin plus RT might be a treatment option regarding tolerability; further evidence should be generated in this setting.