Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

DOI Web Site 1 Citations
  • Maria E. Cabanillas
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • Jonas A. de Souza
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • Susan Geyer
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • Lori J. Wirth
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • Michael E. Menefee
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • Stephen V. Liu
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • Komal Shah
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • John Wright
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.
  • Manisha H. Shah
    Maria E. Cabanillas and Komal Shah, The University of Texas MD Anderson Cancer Center, Houston, TX; Jonas A. de Souza, University of Chicago Medical Center, Chicago, IL; Susan Geyer, University of South Florida, Tampa; Michael E. Menefee, Mayo Clinic Jacksonville, Jacksonville, FL; Lori J. Wirth, Massachusetts General Hospital, Boston, MA; Stephen V. Liu, MedStar Georgetown University Hospital; John Wright, National Cancer Institute, Washington, DC; and Manisha H. Shah, Ohio State University, Columbus, OH.

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<jats:sec><jats:title>Purpose</jats:title><jats:p> Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy. </jats:p></jats:sec>

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