title: Timing of multikinase inhibitor initiation in differentiated thyroid cancer.
abstract: There are limited treatment options for patients with radioactive iodine refractory, progressive differentiated thyroid cancer. Although there is consensus that multikinase inhibitor therapy should be considered in patients with progressive disease with considerable tumor load or symptomatic disease, uncertainty exists on the optimal timing to treat with a multikinase inhibitor, especially for asymptomatic patients. RIFTOS MKI is an international, prospective, open-label, multicenter, noninterventional study with the primary objective to compare the time to symptomatic progression from study entry in asymptomatic patients with radioactive iodine refractory, progressive differentiated thyroid cancer for whom there is a decision to initiate multikinase inhibitors at study entry (cohort 1) with those for whom there is a decision to not initiate multikinase inhibitors at study entry (cohort 2). Secondary endpoints are overall survival and progression-free survival, which will be compared between cohorts 1 and 2. Additional secondary endpoints are postprogression survival from time of symptomatic progression, duration of and response to each systemic treatment regimen and dosing of sorafenib throughout the treatment period. Asymptomatic, multikinase inhibitor-naive patients aged ≥18 years with histologically/cytologically documented differentiated thyroid cancer that is radioactive iodine refractory are eligible. Patients may receive any therapy for differentiated thyroid cancer, including sorafenib or other multikinase inhibitors if indicated and decided on by the treating physician. In total, 700 patients are estimated to be enrolled from >20 countries. Final analysis will be performed once the last enrolled patient has been followed up with for 24 months (ClinicalTrials.gov identifier: Nbib2303444).
authors.affiliation: Department of Otorhinolaryngology: Head and Neck SurgeryAbramson Cancer Center of the University of Pennsylvania, Stellar-Chance Laboratories Mezzanine, Philadelphia, Pennsylvania, USA brosem@mail.med.upenn.edu.
authors.forename: Marcia S
authors.initials: MS
authors.lastname: Brose
authors.affiliation: Department of Internal MedicineRadboud University Nijmegen Medical Center, 463 General Internal Medicine, Nijmegen, Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Smit
authors.affiliation: Department of OncologyNational Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Division of EndocrinologyHospital de Clínicas, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Fabian
authors.initials: F
authors.lastname: Pitoia
authors.affiliation: Bayer HealthCare PharmaceuticalsWhippany, New Jersey, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Fellous
authors.affiliation: Bayer HealthCare PharmaceuticalsWhippany, New Jersey, USA.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: DeSanctis
authors.affiliation: Department of Nuclear Medicine and Endocrine OncologyInstitut Gustave Roussy and Université Paris Saclay, Villejuif, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.affiliation: Department of Endocrine SurgeryOsaka Police Hospital, Tennoujiku, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tori
authors.affiliation: Department of Endocrine SurgeryNippon Medical School Graduate School of Medicine, Bunkyo-Ku, Tokyo, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Sugitani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011804:Quinolines / Q000627:therapeutic use; D016879:Salvage Therapy; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D009536:Niacinamide; D000077157:Sorafenib; C531958:lenvatinib
keywords: differentiated thyroid cancer; multikinase inhibitor; noninterventional; observational; radioactive iodine refractory; sorafenib