title: Clinical trial end points for assessing efficacy of novel therapies for soft-tissue sarcomas.
abstract: Soft-tissue sarcomas (STS) comprise a heterogeneous group of rare malignancies from mesenchymal tissues. Although outcome varies by histology, adults with disseminated metastatic STS have a poor prognosis despite current treatment options. The authors reviewed commonly used clinical end points for STS and discussed which end points may be appropriate for evaluating the clinical benefit of novel targeted therapies. In sarcoma, surrogates for both overall survival, the gold standard end point, and the objective response rate, measured by Response Evaluation Criteria in Solid Tumors, are commonly used. More appropriate end points for evaluating newly targeted agents include progression-free survival and clinical benefit rate. Results from recently completed Phase III trials of two targeted therapies in advanced STS, the mTOR inhibitor ridaforolimus and the multikinase inhibitor pazopanib, should shed light on whether progression-free survival and clinical benefit rate are appropriate end points in advanced STS.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Santa Monica, CA 90404, USA. bchmielowski@mednet.ucla.edu
authors.forename: Bartosz
authors.initials: B
authors.lastname: Chmielowski
authors.forename: Noah
authors.initials: N
authors.lastname: Federman
authors.forename: William D
authors.initials: WD
authors.lastname: Tap
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D057915:Drug Substitution / Q000379:methods; D015507:Drugs, Investigational / Q000494:pharmacology*; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D007191:Indazoles; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D010043:Outcome and Process Assessment, Health Care / Q000379:methods; D011379:Prognosis; D011743:Pyrimidines / Q000494:pharmacology*; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015507:Drugs, Investigational; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C515074:ridaforolimus; C516667:pazopanib; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus