RT Journal Article
T1 Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial.
A1 Tap, William D
A1 Wagner, Andrew J
A1 Schöffski, Patrick
A1 Martin-Broto, Javier
A1 Krarup-Hansen, Anders
A1 Ganjoo, Kristen N
A1 Yen, Chueh-Chuan
A1 Abdul Razak, Albiruni R
A1 Spira, Alexander
A1 Kawai, Akira
A1 Le Cesne, Axel
A1 Van Tine, Brian A
A1 Naito, Yoichi
A1 Park, Se Hoon
A1 Fedenko, Alexander
A1 Pápai, Zsuzsanna
A1 Soldatenkova, Victoria
A1 Shahir, Ashwin
A1 Mo, Gary
A1 Wright, Jennifer
A1 Jones, Robin L
A1 ANNOUNCE Investigators, 
AB Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone. To determine the efficacy of doxorubicin plus olaratumab in patients with advanced/metastatic STS. ANNOUNCE was a confirmatory, phase 3, double-blind, randomized trial conducted at 110 sites in 25 countries from September 2015 to December 2018; the final date of follow-up was December 5, 2018. Eligible patients were anthracycline-naive adults with unresectable locally advanced or metastatic STS, an Eastern Cooperative Oncology Group performance status of 0 to 1, and cardiac ejection fraction of 50% or greater. Patients were randomized 1:1 to receive doxorubicin, 75 mg/m2 (day 1), combined with olaratumab (n = 258), 20 mg/kg in cycle 1 and 15 mg/kg in subsequent cycles, or placebo (n = 251) on days 1 and 8 for up to 8 21-day cycles, followed by olaratumab/placebo monotherapy. Dual primary end points were overall survival with doxorubicin plus olaratumab vs doxorubicin plus placebo in total STS and leiomyosarcoma (LMS) populations. Among the 509 patients randomized (mean age, 56.9 years; 58.2% women; 46.0% with LMS), all were included in the primary analysis and had a median length of follow-up of 31 months. No statistically significant difference in overall survival was observed between the doxorubicin plus olaratumab group vs the doxorubicin plus placebo group in either population (total STS: hazard ratio, 1.05 [95% CI, 0.84-1.30], P = .69, median overall survival, 20.4 months vs 19.7 months; LMS: hazard ratio, 0.95 [95% CI, 0.69-1.31], P = .76, median overall survival, 21.6 months vs 21.9 months). Adverse events of grade 3 or greater reported in 15% or more of total patients with STS were neutropenia (46.3% vs 49.0%), leukopenia (23.3% vs 23.7%), and febrile neutropenia (17.5% vs 16.5%). In this phase 3 clinical trial of patients with advanced STS, treatment with doxorubicin plus olaratumab vs doxorubicin plus placebo resulted in no significant difference in overall survival. The findings did not confirm the overall survival benefit observed in the phase 2 trial. ClinicalTrials.gov Identifier: NCT02451943.
YR 2020
FD 2020
LK http://hdl.handle.net/10668/15335
UL http://hdl.handle.net/10668/15335
LA en
DS RISalud
RD Apr 4, 2025