OR14-5 Salvage therapy with tyrosine kinase inhibitors (TKIs) for differentiated thyroid carcinoma (DTC) after first line sorafenib failure

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR14-Thyroid Cancer: Insights into Diagnosis & Treatment
Clinical
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 12:30 PM
Room 103 (Moscone Center)
Ramona Dadu*1, Mimi I-Nan Hu2, Mouhammed Amir Habra2, Steven Gerard Waguespack2, Anita K Ying2, Naifa Lamki Busaidy2 and Maria Cabanillas2
1Baylor College of Medicine, Houston, TX, 2The University of Texas MD Anderson Cancer Center, Houston, TX
Background:  Treatment with a TKI is considered for metastatic, progressive, iodine-refractory DTC. However, patients will eventually develop progressive disease (PD) or intolerability leading to drug discontinuation. Sorafenib is often used as first line therapy in DTC. For papillary thyroid cancer patients treated with first line sorafenib, previously reported median overall survival (OS) and progression free survival (PFS) were 92 and 54 weeks, respectively(1). Treatment with TKIs with similar mechanism of action after sorafenib failure is common in clinical practice, but no data are available with regards to benefit of sequential treatment. We hypothesize that salvage TKIs use after sorafenib failure represents a viable treatment option in selected patients. With the increasing use of TKIs in clinical practice, this information will be important to physicians who are facing these challenging cases.

Methods: We performed a retrospective analysis of DTC patients who received salvage therapy with TKIs after first line sorafenib failure. Sorafenib failure was defined as PD or unacceptable toxicity leading to drug discontinuation. The objective was to compare the median time on treatment with sorafenib and second line TKIs and to assess the median OS.

Results:  Twenty-one adult patients were identified (12 female, 9 male): 12 follicular, 8 papillary and 1 poorly differentiated carcinoma. Median age at diagnosis was 54 years (range 39-74). The majority had T3 and T4 tumors at diagnosis; median tumor size was 3.5 cm (range 1.8-9.5). Prior treatment included surgery (95%), radioactive iodine (100%), and radiation to the neck (33%). All patients had RAI refractory disease. Prior to sorafenib start, neck disease was present in 17/21 (81%) patients; most common sites of distant metastases included lung in all and bone in 9/21 (43%) patients. Median time from diagnosis to sorafenib start was 48 months (range 4-136). Sorafenib hold and dose reduction was needed in 13/21 (62%) and 10/21 (58%) patients, respectively. The reason for sorafenib discontinuation was PD in 19/21 (90%) and toxicity in 2/21 (10%) patients. Salvage therapy included sunitinib (8), pazopanib (2), vemurafenib (2) and investigational TKIs (9). Median time on treatment with sorafenib and salvage therapy was 46 and 61 weeks respectively (p=0.26). Estimated median OS was 166 weeks.

Conclusions:  Duration of treatment is comparable between first and second line therapy suggesting an added clinical benefit of salvage TKI use after sorafeib failure. The median OS of our group of patients receiving multiple line TKIs after sorafenib failure is higher than previously reported on patients receiving first line sorafenib.  This small retrospective study supports the potential utility of salvage TKI use after sorafenib failure, but further study, including a comparison against a control group and a prospective study, will be required.

(1)Kloos RT et al., J Clin Oncol. 2009 Apr 1;27(10):1675-84

Disclosure: MAH: Clinical Researcher, Eisai. NLB: Clinical Researcher, Bayer, Inc.. MC: Clinical Researcher, Exelixis, Inc., Clinical Researcher, Eisai, Clinical Researcher, Roche Diagnostics, Advisory Group Member, Exelixis, Inc., Advisory Group Member, Eisai. Nothing to Disclose: RD, MINH, SGW, AKY

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm