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Author Notes:

Taofeek K. Owonikoko, owonikokotk2@upmc.edu;Tel.: +412-638-5898

Conception and Design: T.K.O., Z.C. and F.R.K.; Data Generation: All authors (J.E.B., Z.C., C.Z., J.P.O., R.L.F., G.M.M., S.B., S.S., A.Y.C., C.E.S., D.M.S., N.F.S., F.R.K. and T.K.O.); Data Analysis: T.K.O., Z.C. and C.Z.; Manuscript Writing and Approval: All authors (J.E.B., Z.C., C.Z., J.P.O., R.L.F., G.M.M., S.B., S.S., A.Y.C., C.E.S., D.M.S., N.F.S., F.R.K. and T.K.O.). All authors have read and agreed to the published version of the manuscript.

The authors thank patients and family members and the research team members at the participating sites for their support of the study. The authors are grateful to Anthea Hammond for editorial assistance.

T.K.O. received research funding and served on a paid advisory board for Novartis Oncology.

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Research Funding:

This work was supported through funding and study drugs generously provided by Novartis Oncology under award number CRAD001LUS141T.

Research reported in this publication was also supported in part by the Biostatistics and Bioinformatics Shared resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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

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

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Journal Title:

CANCERS

Volume:

Volume 14, Number 11

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Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2022 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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