Cabozantinib Salvage Therapy in Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer

Key Points

  • Cabozantinib produced response in 25% of patients with tyrosine kinase inhibitor–refractory differentiated thyroid cancer, and stable disease was reported in 52%.
  • Median progression-free survival was 12.7 months.

A phase II study has shown that cabozantinib (Cometriq) produces responses in patients with tyrosine kinase inhibitor–refractory differentiated thyroid cancer. The findings were reported by Cabanillas et al in the Journal of Clinical Oncology. MET plays a role in vascular endothelial growth factor receptor (VEGFR) inhibitor resistance. Cabozantinib is a multi–tyrosine kinase inhibitor that blocks MET and VEGFR and is currently approved for use in medullary thyroid cancer.

Study Details

The study included 25 patients with radioiodine-refractory differentiated thyroid cancer who had progression on VEGFR inhibitor therapy, including 21 who had received 1 inhibitor (sorafenib [Nexavar], pazopanib [Votrient], or cediranib) and 4 who had received 2 inhibitors. Patients had a median age of 64 years. Cabozantinib was started at 60 mg/d and could be increased to 80 mg/d in the absence of response.

Response Rates

Among the 25 patients, 7 were treated at 60 mg/d, 4 had escalation to 80 mg/d, and 14 had dose reductions to 40 mg/d (n = 6) or 20 mg/d. Median duration of follow-up was 22.8 months. Response was observed in 10 patients (40%, all partial responses) and was observed at all dose levels; stable disease was observed in 13 patients (52%). Responses were observed only among patients who had received only one prior VEGFR inhibitor.

Median progression-free survival was 12.7 months, with 12- and 24-month progression-free survival rates of 55% and 25%, respectively. Median overall survival was 34.7 months, with 12- and 24-month survival rates of 80% and 66%, respectively.

The most common treatment-related adverse events of any grade (> 40% of patients) were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. The most common treatment-related grade 3 adverse events were hypophosphatemia (16%), fatigue (12%), weight loss (12%), lipase/amylase elevation (12%), and neutropenia (12%). One death (death not otherwise specified) was considered related to study treatment.

The investigators concluded: “Cabozantinib demonstrated clinically significant, durable objective response activity in patients with [radioactive iodine]-refractory [differentiated thyroid cancer] who experienced disease progression while taking prior VEGFR-targeted therapy.”

The study was supported in part by a grant from the International Thyroid Oncology Group.

Manisha H. Shah, MD, of The Ohio State University, is the corresponding author of the Journal of Clinical Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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