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

• Published in: Experimental and Clinical Endocrinology & Diabetes
• Main Authors: Paschke, R, Schlumberger, M, Nutting, C, Jarzab, B, Elisei, R, Siena, S, Bastholt, L, de la Fouchardiere, C, Pacini, F, Shong, YK, Sherman, SI, Smit, J, Kappeler, C, Molnar, I, Brose, MF
• Format: Conference Proceeding
• Language: English
• Published: 12.03.2015
• ISSN: 0947-7349; 1439-3646
• DOI: 10.1055/s-0035-1547632

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.