Cabozantinib Shows Strong Activity in RAI-Refractory Thyroid Cancer

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Cabozantinib showed significant antitumor activity in the treatment of differentiated thyroid cancer that progressed following surgery and radioactive iodine therapy, according to a new phase II study.

Cabozantinib showed significant antitumor activity in the treatment of differentiated thyroid cancer (DTC) that progressed following surgery and radioactive iodine therapy (RAI), according to a new phase II study.

“The recent introduction of targeted therapy with kinase inhibitors for patients with advanced thyroid cancer created a possible path to control the cancers of patients we previously could treat only with supportive care. Our trial shows that cabozantinib also is an active agent and could significantly improve the care of patients with advanced disease,” said Marcia S. Brose, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, in a press release. She presented results of the new trial at the 2018 Multidisciplinary Head and Neck Cancers Symposium, held February 15–17 in Scottsdale, Arizona.

Cabozantinib, a multi–tyrosine kinase inhibitor that targets the VEGF receptor, RET, MET, and AXL, is approved for patients with advanced medullary thyroid cancer and renal cell carcinoma. Some prior early research has suggested it may have activity in RAI-refractory DTC.

The new phase II trial included 35 patients with metastatic RAI-refractory DTC, and no prior treatment with a VEGF receptor inhibitor. Patients had a median age of 65 years, and 49% were male; 66% of the cohort had papillary histology, while 9% had follicular disease and 26% were poorly differentiated.

A total of 19 patients (54%) had a partial response, and another 15 (43%) had stable disease. Nine patients had stable disease for more than 6 months, and the clinical benefit rate (complete and partial responses plus stable disease for at least 6 months) was 80%. The median progression-free survival (PFS) had not yet been reached, and the median time on the study drug was 35 weeks. Nearly all of the patients (34 of 35) experienced some tumor shrinkage.

Dose interruptions or adjustments were required for most patients (23 of 35), and treatment-related adverse events of any grade were reported in all patients. The most common treatment-emergent adverse events included hyperglycemia (80%), diarrhea (77%), malaise/fatigue (74%), and weight loss (71%). Hypertension was the most common grade 3–5 adverse event (14%), followed by increased lipase (9%), pulmonary embolism (6%), and hyponatremia (6%).

“The two kinase inhibitors that are currently FDA approved are used sequentially to improve the PFS of these patients, but as patients ultimately progress, more treatment options are needed, and cabozantinib would seem to be another agent that could provide relief for these patients,” Brose concluded during a press conference. She said that a large, multicenter, phase III trial of the agent is now being designed.

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