A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer

Cancers

Conor E. Steuer¹  Gerald M. McGorisk²  Sumathi Srivatsa³  Stephen Brandt³  James P. Ohr⁴  Julie E. Bauman⁴  Taofeek K. Owonikoko⁴  Amy Y. Chen⁵  Robert L. Ferris⁶  Fadlo R. Khuri⁷  Dong M. Shin⁷  Chao Zhang⁷  Zhengjia Chen⁷  Nabil F. Saba⁷ 

[1] Department of Hematology/Medical Oncology, Emory University, Atlanta, GA 30322, USA;Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA 30322, USA;Department of Medicine, Division of Endocrinology, Emory University, Atlanta, GA 30322, USA;Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA;Department of Otolaryngology, Emory University, Atlanta, GA 30322, USA;Department of Otolaryngology, Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA;Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA;

关键词: thyroid cancer;    somatostatin receptor;    everolimus;    pasireotide;    combination;    medullary carcinoma;   

DOI  :  10.3390/cancers14112639

来源: DOAJ

【 摘 要 】

Purpose: Aberrant mTOR pathway and somatostatin receptor signaling are implicated in thyroid cancer and offer potential therapeutic targets. We assessed the clinical efficacy of everolimus and Pasireotide long-acting release (LAR) in radioiodine-refractory differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC). Patients and methods: Adults with progressive MTC and DTC untreated or treated with no more than one systemic agent were eligible. The trial was designed to establish the most promising regimen and the optimal combination sequence. Patients were randomized to start treatment with single agent everolimus (10 mg QD; Arm A), pasireotide-LAR (60 mg intramuscular injection, Q4 weeks; Arm B), or the combination (Arm C). At initial progression (PFS1), patients on Arm A or B switched to the combination and continued until progression (PFS2). Efficacy was measured by RECIST criteria. Results: Study enrolled 42 patients: median age 65 years; female 17 (40.5%); White 31 (73.8%), African American 6 (14.3%), others 5 (11.9); DTC 32 (76.2%); MTC 10 (23.8%). There was no objective response by RECIST criteria across the three arms. Median and 1-year PFS1 rates were 8.3, 1.8, 8.1 months and 49.9%, 36.4%, 25.0% for Arms A, B, C, respectively. Median and 1-year PFS2 rates were 26.3, 17.5, 8.1 months and 78.4%, 70.0%, 25% for Arms A, B, C, respectively. The most frequent adverse events were anemia, stomatitis, fatigue, hyperglycemia, and hypercholesterolemia. Conclusions: The combination of everolimus and pasireotide-LAR showed promising efficacy over single agent. The delayed combination of everolimus and pasireotide-LAR following progression on single agent everolimus appeared intriguing as a combination strategy.

【 授权许可】

Unknown