Trabectedin and Concurrent Low-Dose Radiotherapy Feasible
Trabectedin concurrent with lowdose radiotherapy is being examined as an option for patients with pulmonary metastatic soft tissue sarcoma (NCT02275286).
In a phase 1 study, long-lasting dimensional responses were seen in 71% of the irradiated lesions. Based on those results, trabectedin (Yondelis) at 1.5 mg/m2 will be the recommended dose for phase 2, according to Javier Martín-Broto, MD, of the Institute of Biomedicine Research (IBIS)-University Hospital Virgen del Rocio/CSIC/University of Seville, Spain, and his colleagues, reporting at CTOS 2018.
For the study, trabectedin was given along with radiotherapy (30 Gy) in 10 fractions (3 Gy/fraction). Three dose levels of trabectedin were administered: -1 (1.1 mg/m2), 1 (1.3 mg/m2), and 2 (1.5 mg/m2). Dose-limiting toxicity was defined as grade 3 or greater events excluding grade 3/4 neutropenia lasting less than 5 days, grade 3 transaminitis if it did not lead to trabectedin delay, and grade 3/4 nausea/vomiting due to inadequate prophylaxis.
Ten of the 18 patients enrolled had synovial sarcoma; 3 had undifferentiated pleomorphic sarcomas, and the other patients had either myxoid liposarcoma, dedifferentiated liposarcoma, G3 not otherwise specified sarcoma, leiomyosarcoma, or malignant peripheral nerve sheath tumor.
Patients received a median of 1 prior line of chemotherapy (range: 0-3). Twelve patients received trabectedin at dose level 1 and 6 patients at dose level 2. Grade 3/4 adverse events were neutropenia, seen in 8 patients; alanine aminotransferase (ALT) elevation, seen in 2 patients; gamma-glutamyl transferase (GGT) elevation, seen in 2 patients; anemia, seen in 2 patients; febrile neutropenia, seen in 1 patient; and pneumonitis, seen in 1 patient.
There were two dose-limiting toxicities: transient grade 4 ALT elevation at the level 1 dose and grade 4 neutropenia for more than 5 days at the level 2 dose.
Based on central radiological review of 17 evaluable patients, 2 patients achieved complete response, 3 had partial responses, 6 had stable disease, and 6 had progressive disease. The local review reported complete responses in 2 patients, partial responses in 5, stable disease in 4, and progressive disease in 6.
Of the irradiated lesions, 71% had long-lasting dimensional responses: 4 completely responded, 8 responded partially, 4 were stable, and 1 progressed.
With a median follow-up of 18 months, median progression-free survival was 2.83 months (95%CI: 2.3-3.3 months). Thirteen patients have died, with a median overall survival of 8.77 months (95%CI: 3.6-13.9) and a 12-month overall survival rate of 48%.
The investigators concluded trabectedin with concurrent radiotherapy was feasible in patients with pulmonary metastatic soft tissue sarcoma regardless of their histologic subtype.