Adding evofosfamide to doxorubicin is not recommended as a first-line treatment for patients with advanced soft-tissue sarcoma, according to a study published in The Lancet Oncology.1
The median 2-year overall survival (OS) among patients with newly diagnosed metastatic sarcoma is 20% to 30%. The standard first-line therapy in this setting is doxorubicin, which confers a median OS of 12 to 17 months. Phase 2 trial data suggest that adding evofosfamide to doxorubicin-based therapy may improve outcomes among patients with unresectable advanced or metastatic sarcoma.
For this phase 3, randomized trial (ClinicalTrials.gov Identifier: NCT01440088), researchers assessed 779 patients with sarcoma for eligibility, of whom 640 were assigned to receive doxorubicin alone (323 patients) or doxorubicin plus evofosfamide (317 patients). Patient characteristics were similar between the 2 groups.
The OS endpoint was not reached. Median OS was 18.4 months with evofosfamide plus doxorubicin vs 19 months with doxorubicin alone (P = .527).
Subgroup analyses did not show a significant survival benefit with the drug combination except among patients with synovial sarcoma, for whom median OS was 22.1 months with the combination vs 9.4 months with doxorubicin alone. There were, however, only 33 patients with synovial sarcoma enrolled in this trial.
Forty-six percent of patients who received evofosfamide and 32% of patients in the doxorubicin-only group had serious adverse events. Five patients in the combination group and 1 patient in the doxorubicin-only group died from treatment related causes.
While the study did not support incorporating evofosfamide into the first-line treatment of sarcoma, the authors recommended an “additional study in synovial sarcoma,” and noted that “[we] think the majority of the sarcoma community would be in favour and supportive of such a trial.”
- Tap WD, Papai Z, Van Tine BA, et al. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. doi: 10.1016/S1470-2045(17)30381-9 [Epub ahead of print]