Exp Clin Endocrinol Diabetes 2015; 123 - P03_05
DOI: 10.1055/s-0035-1547632

Exploratory analysis of outcomes for patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer (RAI-RDTC) receiving open-label Sorafenib post-progression on the phase III decision trial

R Paschke 1, M Schlumberger 2, C Nutting 3, B Jarzab 4, R Elisei 5, S Siena 6, L Bastholt 7, C de la Fouchardiere 8, F Pacini 9, YK Shong 10, SI Sherman 11, J Smit 12, C Kappeler 13, I Molnar 14, MF Brose 15
  • 1University of Leipzig; Department of Internal Medicine, Neurology and Dermatology; Division of Endocrinology and Nephrology
  • 2Department of Nuclear Medicine and Endocrine Oncology; Institut Gustave Roussy and University Paris Sud
  • 3Royal Marsden Hospital, London
  • 4Msc Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Department of Nuclear Medicine and Endocrine Oncology
  • 5Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  • 6Ospedale Niguarda Ca' Granda, Milan
  • 7Odense University Hospital, Odense C, Denmark
  • 8Consortium Cancer Thyroïdien, Hospices Civils-Centre Anticancéreux, Lyon, France
  • 9Section of Endocrinology, University of Siena, Siena, Italy – Siena
  • 10Asan Medical Center; University of Ulsan College of Medicine
  • 11Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
  • 12Department of General Internal Medicine, Radboud University Nijmegen Medical Centre
  • 13Bayer Pharma AG, Berlin, Germany
  • 14Bayer Healthcare Pharmaceuticals, Whippany, Nj
  • 15Department of Otorhinolaryngology: Head and Neck Surgery, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pa, USA

Background:

RAI-rDTC patients treated with sorafenib (SOR) in the phase III placebo (PLC)-controlled DECISION trial had significantly improved progression-free survival (PFS). Patients who progressed in the double-blind (DB) period were unblinded and at the investigator's discretion allowed to receive open-label (OL) SOR and then followed for subsequent disease progression (PFS2).

Methods:

PFS2, an exploratory endpoint, was defined as time from new baseline until centrally assessed progression or death during or after OL-SOR treatment.

Results:

A total of 207 patients were randomized to sorafenib (DB-SOR) and 210 to placebo (DB-PLC). 150 PLC patients crossed over to OL-SOR at progression; 137 evaluable for efficacy (PLC-SOR). 55 DB-SOR patients continued OL-SOR at progression; 46 evaluable for efficacy (SOR-SOR). The PLC-SOR and SOR-SOR patients had poorer risk features at enrollment compared to patients not assessed for PFS2.

Partial responses in the DB-SOR and PLC-SOR patients were 12.2% and 9.5%, respectively. Among SOR-SOR patients with progression events in both periods, PFS2 was more than two-fold longer than PFS1 in 22%. The median treatment duration for SOR patients receiving DB and OL treatment was 56.9 weeks. Adverse events were similar for PLC-SOR and DB-SOR patients. For SOR-SOR patients, diarrhea and hand-foot skin reactions were reduced compared to the DB-SOR treatment period.

Conclusions:

PFS2 for the subset of PLC patients who crossed over to OL-SOR was longer (9.6 months) than PFS1 (5.3 months). Continuation of SOR after progression needs to be explored further.