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

• Authors: Stephen Brandt, Emory University; Sumathi Srivatsa, Emory University; Gerard McGorisk, Emory University; Dong Shin, Emory University; Nabil Saba, Emory University; Fadlo Khuri, Emory University; Taofeek Owonikoko, Emory University; Zhengjia Chen, Emory University; Amy Chen, Emory University; Conor Steuer, Emory University; JE Bauman, University of Pittsburgh; C Zhang, Emory University; JP Ohr, University of Pittsburgh; RL Ferris, University of Pittsburgh
• Journal Title: CANCERS
• Volume: Volume 14, Number 11
• Publisher: MDPI | 2022-06-01
• Type of Work: Article
• Publisher DOI: http://doi.org/10.3390/cancers14112639
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; thyroid cancer; somatostatin receptor; everolimus; pasireotide; combination; medullary carcinoma; TOR Serine-Threonine Kinases; MAMMALIAN TARGET; DOUBLE-BLIND; MEDULLARY; ACTIVATION; OCTREOTIDE; CARCINOMA; RAPAMYCIN; AKT; SOM230; PROLIFERATION

Abstract

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.