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Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial.

dc.contributor.authorTap, William D
dc.contributor.authorWagner, Andrew J
dc.contributor.authorSchöffski, Patrick
dc.contributor.authorMartin-Broto, Javier
dc.contributor.authorKrarup-Hansen, Anders
dc.contributor.authorGanjoo, Kristen N
dc.contributor.authorYen, Chueh-Chuan
dc.contributor.authorAbdul-Razak, Albiruni R
dc.contributor.authorSpira, Alexander
dc.contributor.authorKawai, Akira
dc.contributor.authorLe-Cesne, Axel
dc.contributor.authorVan-Tine, Brian A
dc.contributor.authorNaito, Yoichi
dc.contributor.authorPark, Se Hoon
dc.contributor.authorFedenko, Alexander
dc.contributor.authorPapai, Zsuzsanna
dc.contributor.authorSoldatenkova, Victoria
dc.contributor.authorShahir, Ashwin
dc.contributor.authorMo, Gary
dc.contributor.authorWright, Jennifer
dc.contributor.authorJones, Robin L
dc.contributor.groupANNOUNCE Investigators
dc.date.accessioned2023-02-08T14:45:01Z
dc.date.available2023-02-08T14:45:01Z
dc.date.issued2020-04-07
dc.description.abstractPatients 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.
dc.description.versionSi
dc.identifier.citationTap WD, Wagner AJ, Schöffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, et al. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1266-1276.
dc.identifier.doi10.1001/jama.2020.1707
dc.identifier.essn1538-3598
dc.identifier.pmcPMC7139275
dc.identifier.pmid32259228
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139275/pdf
dc.identifier.unpaywallURLhttps://jamanetwork.com/journals/jama/articlepdf/2764181/jama_tap_2020_oi_200020.pdf
dc.identifier.urihttp://hdl.handle.net/10668/15335
dc.issue.number13
dc.journal.titleJAMA
dc.journal.titleabbreviationJAMA
dc.language.isoen
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.number1266-1276
dc.provenanceRealizada la curación de contenido 29/04/2025
dc.publisherAmerican Medical Association
dc.pubmedtypeClinical Trial, Phase III
dc.pubmedtypeComparative Study
dc.pubmedtypeJournal Article
dc.pubmedtypeMulticenter Study
dc.pubmedtypeRandomized Controlled Trial
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.publisherversionhttps://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.1707
dc.rights.accessRightsRestricted Access
dc.subjectAntibiotics, Antineoplastic
dc.subjectAntibodies, Monoclonal
dc.subjectDoxorubicin
dc.subjectDrug Administration Schedule
dc.subjectProportional Hazards Models
dc.subjectYoung Adult
dc.subject.decsDoxorrubicina
dc.subject.decsPacientes
dc.subject.decsSobrevida
dc.subject.decsLeiomiosarcoma
dc.subject.decsNeutropenia febril
dc.subject.decsTerapéutica
dc.subject.decsNeutropenia
dc.subject.decsMujeres
dc.subject.decsAntraciclinas
dc.subject.decsLeucopenia
dc.subject.decsEnsayo clínico
dc.subject.decsSarcoma
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols
dc.subject.meshDouble-Blind Method
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPlacebos
dc.subject.meshSarcoma
dc.subject.meshSurvival Analysis
dc.titleEffect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number323
dspace.entity.typePublication

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