Results of a randomized phase II trial of 2nd-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib: Japan Clinical Oncology Group study JCOG1802 (2ND-STEP).

11551 Background: Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD) are the candidates of second-line chemotherapy for advanced soft tissue sarcomas (STS), although there is no clear evidence showing which is better among those agents. This clinical trial aims to determine the most promising regimen among trabectedin, eribulin, and pazopanib as the test arm regimen in the future phase III trial of the second-line treatment for patients with advanced STS. Methods: This study, JCOG1802, is a multicenter randomized phase II selection design trial comparing trabectedin (1.2 mg/m 2 IV, every 3 weeks), eribulin (1.4 mg/m 2 IV, days 1 and 8, every 3 weeks) and pazopanib (800 mg PO, everyday) for patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. Eligibility criteria include 16 years old or older, ECOG performance status of 0–2, unresectable and/or metastatic STS, an exacerbation within 6 months prior to registration, histological diagnosis of STS other than Ewing sarcoma, well-differentiated liposarcoma and myxoid liposarcoma, a history of chemotherapy of doxorubicin-based regimen for STS, and sufficient organ function. Primary endpoint is progression-free survival (PFS), and secondary endpoints include overall survival (OS), disease-control rate (DCR), response rate (RR), and adverse events. The planned total sample size was set at 120 patients to select the most promising regimen with a probability of at least 80%, assuming a median PFS of 3 months in the worst regimen and 4 months in the best regimen. The regimen demonstrating the most favorable point estimate of hazard ratio for PFS is chosen for the subsequent phase III trial. Results: From December 2019 to March 2023, 120 patients with advanced STS were enrolled (31 with leiomyosarcomas, 26 with liposarcomas, 18 with translocation-related sarcomas, and 45 with others) and randomized. Median PFS for trabectedin was 2.9 months (95% CI 1.3-5.3), for eribulin was 2.2 months (1.5-3.8), and for pazopanib was 3.7 months (2.6-5.2), respectively. The hazard ratios for eribulin and pazopanib compared to trabectedin were 1.22 (0.77-1.94) and 0.99 (0.63-1.56), respectively. Median OS for trabectedin was 14.8 months (10.8-29.1), for eribulin was 13.3 months (7.6-20.1), and for pazopanib was 15.7 months (9.8-not estimable). DCR for trabectedin was 50.0% (32.4-67.6), for eribulin was 34.3% (19.1-52.2), and for pazopanib was 64.9% (47.5-79.8). Conclusions: Pazopanib showed the best PFS and OS as the second-line treatment for patients with advanced STS among trabectedin, eribulin, and pazopanib. A phase III trial comparing GD with pazopanib is planned as the next step. Clinical trial information: jRCTs031190152 .