Randomized Phase 3, Multicenter, Open-Label Study Comparing Evofosfamide (EVO) in Combination with Doxorubicin (D) versus D Alone in Patients with Advanced Soft-Tissue Sarcoma (STS): Study TH-CR-406/SARC021
This randomized phase 3 study compared the efficacy and safety of evofosfamide (EVO) plus doxorubicin (D) with D alone in patients with locally advanced unresectable or metastatic STS previously untreated with chemotherapy for advanced disease. Patients on EVO+D could receive EVO alone after 6 cycles. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), overall response rate (ORR), and safety.
From September 2011 to January 2014, 640 patients were randomized: 317 EVO+D, 323 D; 621 patients were treated. Baseline characteristics were balanced. The median age was 59 years (range, 18-89 years); 57% ECOG 0; 36% leiomyosarcoma, 17% liposarcoma, and 12% undifferentiated pleomorphic sarcoma.
The primary end point, OS, was not met. Median OS was 18.4 months for EVO+D and 19.0 months for D alone. ORR was 28% and 18%, respectively. Median PFS was 6.3 months and 6.0 months, respectively.
The most common grade 3 to 5 adverse events (AEs) were anemia (35%), neutropenia (33%), and leukopenia (18%). Febrile neutropenia occurred in 18% of patients taking EVO+D and 11% taking D. AEs leading to death occurred in 2.6% and 1.0%, respectively.
Although ORR was significantly higher, the combination of EVO+D did not significantly improve OS or PFS. The safety profile was consistent with previous reports.
Tap W, et al. CTOS 2016. Abstract 2554705. P2 Poster 94.