Trabectedin and radiotherapy in advanced sarcoma: Experience of a reference center

Background: In patients with advanced soft tissue sarcomas (STS) there is low probability to obtain tumor shrinkage with second-line drugs. That means that patients requiring volumetric response to palliative relief have few therapeutic options since active second-line drugs in STS exhibit less than 10% of RECIST response. Trabectedin (T) has shown to be synergistic with radiation therapy (RT) in preclinical experiments. Additionally, a substantial activity of T+RT has recently been reported in a phase I trial with 71% of overall response rate (ORR) in the irradiated nodules. Methods: Cases with advanced STS treated with T at standard dose of 1.5 mg/m2 24-h infusion and RT 30-39 Gy (3 Gy per fraction) were collected for this retrospective series from one sarcoma reference center. RT was started 24 h later the trabectedin initiation. ORR according to RECIST 1.1, progression free survival (PFS) and overall survival (OS) were analized. Results: Twenty patients with median age 51 (27-77) and male/female 9/11 were selected. STS subtypes were uterine and somatic leiomyosarcoma 5(25%) and 4 (20%) respectively, high grade myxoid liposarcoma 4 (20%) and non-L STS 7 (35%). All but one patient received previous systemic lines, 2 (0-6). Response assessment was, 5 (25%) PR, 9 (45%) SD and 6 (30%) PD. Considering only radiated lesions, response evaluation was as follows: PR 5 (25%), SD 13 (65%) and 2 (10%) PD. There were 8/12 minor responses. Patients with non-L sarcomas also had disease control (1 myxofibrosarcoma, 2 sarcoma NOS achieved minor responses, 1 fibrosarcoma, 1 malignant peripheral nerve sleath tumor, 1 synovial sarcoma with SD). There were not toxic deaths and only one G3 SAE (transaminitis). No dose-reductions or interruptions were registered. With a median follow-up of 11.2 mos (4.4-36), there were 11 progression and 6 death events. The median of PFS was 9.9 months (6.5-13.2 months) while the median OS has not been reached. Conclusions: T + RT have shown relevant clinical activity in advanced STS, whatever the histotype and location. In 70% of cases there was some shrinkage in radiated lesions bringing up the opportunity of better disease control. Both ORR and PFS were clearly superior with T + RT than historical results obtained with T alone. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: N. Hindi: Research funding to institution: Eisai, Novartis, PharmaMar; Travel funding: PharmaMar. J. Martin-Broto: Advisory: PharmaMar; Research funding to institution: Eisai, Novartis, PharmaMar; Travel funding: PharmaMar. All other authors have declared no conflicts of interest.