Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments

Laura D. Locati, Lisa Licitra, Laura Agate, Sai Hong I Ou, Andree Boucher, Barbara Jarzab, Shukui Qin, Madeleine A. Kane, Lori J. Wirth, Connie Chen, Sinil Kim, Antonella Ingrosso, Yazdi K. Pithavala, Paul Bycott, Ezra E W Cohen

Research output: Contribution to journalArticle

Abstract

BACKGROUND In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed. METHODS Patients (N=52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire. RESULTS The overall ORR was 35% (18 partial responses), and 18 patients had stable disease for ≥16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade ≥3 adverse events (>5%) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed. CONCLUSIONS Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer. Cancer 2014;120:2694-2703.

Original languageEnglish
Pages (from-to)2694-2703
Number of pages10
JournalCancer
Volume120
Issue number17
DOIs
Publication statusPublished - Sep 1 2014

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Thyroid Neoplasms
Pharmacokinetics
Quality of Life
Disease-Free Survival
Safety
Therapeutics
Equipment and Supplies
Survival
Hypocalcemia
Myalgia
Appetite
Iodine
Causality
Dyspnea
Fatigue
axitinib
Diarrhea
Extremities
Hypertension
Weights and Measures

Keywords

  • axitinib
  • MD Anderson Symptom Inventory
  • metastatic disease
  • pharmacodynamic
  • pharmacokinetic
  • quality of life
  • radioactive iodine-refractory
  • thyroid cancer
  • tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Treatment of advanced thyroid cancer with axitinib : Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. / Locati, Laura D.; Licitra, Lisa; Agate, Laura; Ou, Sai Hong I; Boucher, Andree; Jarzab, Barbara; Qin, Shukui; Kane, Madeleine A.; Wirth, Lori J.; Chen, Connie; Kim, Sinil; Ingrosso, Antonella; Pithavala, Yazdi K.; Bycott, Paul; Cohen, Ezra E W.

In: Cancer, Vol. 120, No. 17, 01.09.2014, p. 2694-2703.

Research output: Contribution to journalArticle

Locati, LD, Licitra, L, Agate, L, Ou, SHI, Boucher, A, Jarzab, B, Qin, S, Kane, MA, Wirth, LJ, Chen, C, Kim, S, Ingrosso, A, Pithavala, YK, Bycott, P & Cohen, EEW 2014, 'Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments', Cancer, vol. 120, no. 17, pp. 2694-2703. https://doi.org/10.1002/cncr.28766
Locati, Laura D. ; Licitra, Lisa ; Agate, Laura ; Ou, Sai Hong I ; Boucher, Andree ; Jarzab, Barbara ; Qin, Shukui ; Kane, Madeleine A. ; Wirth, Lori J. ; Chen, Connie ; Kim, Sinil ; Ingrosso, Antonella ; Pithavala, Yazdi K. ; Bycott, Paul ; Cohen, Ezra E W. / Treatment of advanced thyroid cancer with axitinib : Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. In: Cancer. 2014 ; Vol. 120, No. 17. pp. 2694-2703.
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abstract = "BACKGROUND In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed. METHODS Patients (N=52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire. RESULTS The overall ORR was 35{\%} (18 partial responses), and 18 patients had stable disease for ≥16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade ≥3 adverse events (>5{\%}) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed. CONCLUSIONS Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer. Cancer 2014;120:2694-2703.",
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T1 - Treatment of advanced thyroid cancer with axitinib

T2 - Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments

AU - Locati, Laura D.

AU - Licitra, Lisa

AU - Agate, Laura

AU - Ou, Sai Hong I

AU - Boucher, Andree

AU - Jarzab, Barbara

AU - Qin, Shukui

AU - Kane, Madeleine A.

AU - Wirth, Lori J.

AU - Chen, Connie

AU - Kim, Sinil

AU - Ingrosso, Antonella

AU - Pithavala, Yazdi K.

AU - Bycott, Paul

AU - Cohen, Ezra E W

PY - 2014/9/1

Y1 - 2014/9/1

N2 - BACKGROUND In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed. METHODS Patients (N=52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire. RESULTS The overall ORR was 35% (18 partial responses), and 18 patients had stable disease for ≥16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade ≥3 adverse events (>5%) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed. CONCLUSIONS Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer. Cancer 2014;120:2694-2703.

AB - BACKGROUND In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed. METHODS Patients (N=52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire. RESULTS The overall ORR was 35% (18 partial responses), and 18 patients had stable disease for ≥16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade ≥3 adverse events (>5%) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed. CONCLUSIONS Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer. Cancer 2014;120:2694-2703.

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KW - MD Anderson Symptom Inventory

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KW - pharmacokinetic

KW - quality of life

KW - radioactive iodine-refractory

KW - thyroid cancer

KW - tyrosine kinase inhibitor

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