A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer
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 med...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/11/2639 |
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| author | Julie E. Bauman Zhengjia Chen Chao Zhang James P. Ohr Robert L. Ferris Gerald M. McGorisk Stephen Brandt Sumathi Srivatsa Amy Y. Chen Conor E. Steuer Dong M. Shin Nabil F. Saba Fadlo R. Khuri Taofeek K. Owonikoko |
| author_facet | Julie E. Bauman Zhengjia Chen Chao Zhang James P. Ohr Robert L. Ferris Gerald M. McGorisk Stephen Brandt Sumathi Srivatsa Amy Y. Chen Conor E. Steuer Dong M. Shin Nabil F. Saba Fadlo R. Khuri Taofeek K. Owonikoko |
| author_sort | Julie E. Bauman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:28:03Z |
| format | Article |
| id | doaj.art-b381ba6c41424ff5b695c08317bcd8cb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:28:03Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b381ba6c41424ff5b695c08317bcd8cb2023-11-23T13:48:40ZengMDPI AGCancers2072-66942022-05-011411263910.3390/cancers14112639A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid CancerJulie E. Bauman0Zhengjia Chen1Chao Zhang2James P. Ohr3Robert L. Ferris4Gerald M. McGorisk5Stephen Brandt6Sumathi Srivatsa7Amy Y. Chen8Conor E. Steuer9Dong M. Shin10Nabil F. Saba11Fadlo R. Khuri12Taofeek K. Owonikoko13Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USAWinship Cancer Institute of Emory University, Atlanta, GA 30322, USAWinship Cancer Institute of Emory University, Atlanta, GA 30322, USADepartment of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Otolaryngology, Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Medicine, Division of Cardiology, Emory University, Atlanta, GA 30322, USADepartment of Medicine, Division of Endocrinology, Emory University, Atlanta, GA 30322, USADepartment of Medicine, Division of Endocrinology, Emory University, Atlanta, GA 30322, USADepartment of Otolaryngology, Emory University, Atlanta, GA 30322, USADepartment of Hematology/Medical Oncology, Emory University, Atlanta, GA 30322, USAWinship Cancer Institute of Emory University, Atlanta, GA 30322, USAWinship Cancer Institute of Emory University, Atlanta, GA 30322, USAWinship Cancer Institute of Emory University, Atlanta, GA 30322, USADepartment of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USAPurpose: 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.https://www.mdpi.com/2072-6694/14/11/2639thyroid cancersomatostatin receptoreverolimuspasireotidecombinationmedullary carcinoma |
| spellingShingle | Julie E. Bauman Zhengjia Chen Chao Zhang James P. Ohr Robert L. Ferris Gerald M. McGorisk Stephen Brandt Sumathi Srivatsa Amy Y. Chen Conor E. Steuer Dong M. Shin Nabil F. Saba Fadlo R. Khuri Taofeek K. Owonikoko A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer Cancers thyroid cancer somatostatin receptor everolimus pasireotide combination medullary carcinoma |
| title | A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer |
| title_full | A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer |
| title_fullStr | A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer |
| title_full_unstemmed | A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer |
| title_short | A Multicenter Randomized Phase II Study of Single Agent Efficacy and Optimal Combination Sequence of Everolimus and Pasireotide LAR in Advanced Thyroid Cancer |
| title_sort | multicenter randomized phase ii study of single agent efficacy and optimal combination sequence of everolimus and pasireotide lar in advanced thyroid cancer |
| topic | thyroid cancer somatostatin receptor everolimus pasireotide combination medullary carcinoma |
| url | https://www.mdpi.com/2072-6694/14/11/2639 |
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