Abstract 2827: Association between new onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor (TKI) therapy in phase I clinical trials
Authors: Bilen Mehmet Asim , Patel Amy , Hess Kenneth R. , Munoz Javier , Busaidy Naifa , Abdelrahim Maen , Wheler Jennifer , Janku Filip , Falchook Gerald S. , Hong David S. , Meric-Bernstam Funda , Habra Mohammed A. , Naing Aung 
Published: May 2015

Abstract
Background: TKIs are a new class of novel cancer drugs that represent a significant advance in cancer therapy. TKI-induced thyroid dysfunction has been identified as an important but potentially manageable toxicity of targeted therapy. Relationship between new onset hypothyroidism and clinical response in patients with advanced cancers treated with TKI treatment was evaluated.
Methods: We retrospectively reviewed 410 patients from 5 clinical trials treated with therapy that included at least one TKIstarting January, 2006. Patients with preexisting thyroid disease including thyroid cancer, hypo or hyperthyroidism were excluded. Analysis of 198 patients was performed. Response was determined by RECIST 1.0. Clinical benefit described as complete response or partial response or stable disease &gt; 4 months. Multivariable Logistic Regression Analysis was used to correlate new onset hypothyroidism with clinical benefit.
Results: The median age was 58 years (13 to 85); 56% of patients were female. 27% (53/198) of patients developed hypothyroidism after therapy. Clinical benefit rates were 51% in patients with new onset hypothyroidism versus 34% in patients without hypothyroidism. In the univariate model, the odds ratio (OR) for patients who had new onset hypothyroidism was 2.0 (95% CI: 1.0, 3.7; P=0.038), suggesting they were 2 times more likely to have a clinical benefit than were patients without hypothyroidism. We grouped tumor types into two classes (good risk (breast, gyn, CRC, lung, H/N, GU, Biliary, HCC: 53/114= 46% clinical benefit) and poor risk (melanoma, pancreas, upper GI, others: 24/84= 29% clinical benefit)) based on the proportion of patients experiencing clinical benefit. When adjusted for tumor class, age (&gt;50 years old), sex, the OR was 2.6 (95% CI: 1.3, 5.3; P=0.007) (Table).
Conclusions: New onset hypothyroidism is a positive prognostic indicator for favorable clinical benefit in patients who received TKI treatment.
TableVariableContrastOR (95% CI)*p-valueHypothyroidYes vs. No2.6 (1.3, 5.3)0.007SexMale vs. Female0.8 (0.4, 1.6)0.58Age&gt;50 vs. ≤501.5 (0.7, 3.0)0.3Tumor ClassPoor vs. Good0.4 (0.2, 0.7)0.004*OR &gt; 1 indicates factor increases probability of clinical benefit
Citation Format: Mehmet Asim Bilen, Amy Patel, Kenneth R. Hess, Javier Munoz, Naifa Busaidy, Maen Abdelrahim, Jennifer Wheler, Filip Janku, Gerald S. Falchook, David S. Hong, Funda Meric-Bernstam, Mohammed A. Habra, Aung Naing. Association between new onset hypothyroidism and clinical response in patients treated with tyrosine kinase inhibitor (TKI) therapy in phase I clinical trials. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2827. doi:10.1158/1538-7445.AM2014-2827