A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer

Keith C. Bible, Vera Jean Suman, Michael E. Menefee, Robert Christian Smallridge, Julian R Molina, William J. Maples, Nina J. Karlin, Anne M. Traynor, Priya Kumar, Boon Cher Goh, Wan Teck Lim, Ayoko R. Bossou, Crescent R. Isham, Kevin P. Webster, Andrea K. Kukla, Carolyn Bieber, Jill K. Burton, Pamela Harris, Charles Erlichman

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Design/Setting/Patients/Interventions/ Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45-77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatmentrelated tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC.

Original languageEnglish (US)
Pages (from-to)3179-3184
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number9
DOIs
StatePublished - Sep 2012

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Tumors
Toxicity
Vascular Endothelial Growth Factor Receptor
Heterografts
Phosphotransferases
Tracheitis
Radiation
Hypertension
pazopanib
Anaplastic Thyroid Carcinoma
National Cancer Institute (U.S.)
Thyroid Neoplasms
Mouth
Disease Progression
Arm
Outcome Assessment (Health Care)
Hemorrhage
Pain
Survival
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer. / Bible, Keith C.; Suman, Vera Jean; Menefee, Michael E.; Smallridge, Robert Christian; Molina, Julian R; Maples, William J.; Karlin, Nina J.; Traynor, Anne M.; Kumar, Priya; Goh, Boon Cher; Lim, Wan Teck; Bossou, Ayoko R.; Isham, Crescent R.; Webster, Kevin P.; Kukla, Andrea K.; Bieber, Carolyn; Burton, Jill K.; Harris, Pamela; Erlichman, Charles.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 9, 09.2012, p. 3179-3184.

Research output: Contribution to journalArticle

Bible, KC, Suman, VJ, Menefee, ME, Smallridge, RC, Molina, JR, Maples, WJ, Karlin, NJ, Traynor, AM, Kumar, P, Goh, BC, Lim, WT, Bossou, AR, Isham, CR, Webster, KP, Kukla, AK, Bieber, C, Burton, JK, Harris, P & Erlichman, C 2012, 'A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 9, pp. 3179-3184. https://doi.org/10.1210/jc.2012-1520
Bible, Keith C. ; Suman, Vera Jean ; Menefee, Michael E. ; Smallridge, Robert Christian ; Molina, Julian R ; Maples, William J. ; Karlin, Nina J. ; Traynor, Anne M. ; Kumar, Priya ; Goh, Boon Cher ; Lim, Wan Teck ; Bossou, Ayoko R. ; Isham, Crescent R. ; Webster, Kevin P. ; Kukla, Andrea K. ; Bieber, Carolyn ; Burton, Jill K. ; Harris, Pamela ; Erlichman, Charles. / A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 9. pp. 3179-3184.
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abstract = "Context/Objectives: Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC). Design/Setting/Patients/Interventions/ Outcome Measures: Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90{\%} chance of detecting a response rate of >20{\%} at the 0.10 significance level when the true response rate is >5{\%}), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response. Results: Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7{\%} were female, median age was 66 yr (range 45-77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13{\%}) and pharyngolaryngeal pain (13{\%}). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatmentrelated tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease. Conclusions: Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC.",
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AU - Bible, Keith C.

AU - Suman, Vera Jean

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AU - Smallridge, Robert Christian

AU - Molina, Julian R

AU - Maples, William J.

AU - Karlin, Nina J.

AU - Traynor, Anne M.

AU - Kumar, Priya

AU - Goh, Boon Cher

AU - Lim, Wan Teck

AU - Bossou, Ayoko R.

AU - Isham, Crescent R.

AU - Webster, Kevin P.

AU - Kukla, Andrea K.

AU - Bieber, Carolyn

AU - Burton, Jill K.

AU - Harris, Pamela

AU - Erlichman, Charles

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