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

• Published in: Cancer Vol. 120; no. 17; pp. 2694 - 2703
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 01.09.2014
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; axitinib; Biological and medical sciences; Carcinoma, Papillary - drug therapy; Carcinoma, Papillary - mortality; Carcinoma, Papillary - secondary; Diarrhea - chemically induced; Disease-Free Survival; Endocrinopathies; Female; Humans; Imidazoles - adverse effects; Imidazoles - pharmacokinetics; Imidazoles - therapeutic use; Indazoles - adverse effects; Indazoles - pharmacokinetics; Indazoles - therapeutic use; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - secondary; Male; Malignant tumors; MD Anderson Symptom Inventory; Medical sciences; metastatic disease; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); pharmacodynamic; pharmacokinetic; Quality of Life; radioactive iodine‐refractory; thyroid cancer; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - mortality; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Treatment Outcome; Tumors; tyrosine kinase inhibitor; Endocrinopathy; Antineoplastic agent; MD Anderson Symptom Inventory; Metastasis; Cancerology; Phase II trial; Axitinib; Advanced stage; pharmacokinetic; Iodine; Human; Treatment resistance; Pharmacodynamics; Tyrosine kinase inhibitor; metastatic disease; Thyroid diseases; Malignant tumor; Indazole derivatives; Biological activity; Quality of life; radioactive iodine-refractory; Symptomatology; Thyroid cancer; Treatment; pharmacodynamic; Pharmacokinetics; Inventory; Cancer; thyroid cancer; tyrosine kinase inhibitor; quality of life; axitinib
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28766

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. © 2014 American Cancer Society. This phase 2 trial confirms the clinical activity and favorable safety profile of axitinib in patients with advanced thyroid cancer. Pharmacokinetic/pharmacodynamic analyses suggest that patients with greater axitinib exposure may have longer progression‐free survival, and an assessment of patient‐reported outcomes indicates that quality of life is maintained during axitinib therapy.