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Cabozantinib induces antitumor activity for radioiodine-refractory thyroid cancer
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First-line cabozantinib reduced tumor size among patients with radioactive iodine-refractory differentiated thyroid cancer, according to results from a phase 2 trial presented at the Multidisciplinary Head and Neck Cancers Symposium.
“In the last 5 years, two FDA-approved agents have improved the situation for these patients; both sorafenib [Nexavar, Bayer] and lenvatinib [Lenvima, Eisai] have shown activity in increasing PFS,” Marcia S. Brose, MD, PhD, associate professor in the department of otorhinolaryngology: head and neck surgery and the director of Center for Rare Cancers and Personalized Therapy at the Perelman School of Medicine at University of Pennsylvania, said during a press conference. “However, the responses are not durable, and toxicities may eventually limit their efficacy. So, additional treatment options are still needed for these patients who have a pretty good performance status even after first- or second-line therapy.”
Cabozantinib (Cometriq/Cabometyx, Exelixis) — a multi-tyrosine kinase inhibitor that targets VEGF receptor kinase, RET, MET and AXL — is approved for patients with medullary thyroid cancer and advanced renal cell carcinoma.
Brose and colleagues enrolled 35 patients with metastatic, radioactive iodine-refractory, unresectable or locally advanced thyroid cancer from March 2014 to August 2017. Patients received first-line cabozantinib 60 mg per day. Histology types included papillary (63%), poorly differentiated (29%) and Hürthle cell (9%).
Median time on the study was 35 weeks (range, 3-197). Analysis included 30 patients, and 16 patients remained enrolled in the study as of Feb. 6.
Fifty-three percent of patients achieved a partial response with durations ranging from 11 weeks to more than 174 weeks. Results showed 47% of patients had stable disease, with a duration ranging from 8 weeks to more than 119 weeks. Median PFS had not been reached.
Median time to progression was 35 weeks among the six patients who progressed.
A majority of patients (n = 23) required a dose reduction.
Treatment-related adverse events of any grade occurred among all patients. Grade 1 and grade 2 adverse events included hyperglycemia (80%), diarrhea (77%), malaise/fatigue (74%) and weight loss (71%). Grade 3 or higher adverse events included hypertension (14%), increased lipase (9%), weight loss (6%), pulmonary embolism (6%) and hyponatremia (6%).
“The two kinase inhibitors that are approved are currently used sequentially to improve the PFS of these patients, but if patients ultimately progress, more treatment options are needed and cabozantinib would seem to be another agent that could provide relief for these patients,” Brose said. “It was well tolerated, with mostly grade 1 and grade 2 adverse events. No unexpected toxicities were identified. Cabozantinib is an active agent and merits additional study in a large multicenter phase 3 trial to determine efficacy [among] patients with [radioactive iodine]-refractory differentiated thyroid cancer, the design of which is currently underway.” – by Cassie Homer
Reference:
Brose MS, et al. Abstract 8. Presented at Multidisciplinary Head and Neck Cancers Symposium; Feb. 15-17, 2018; Scottsdale, Ariz.
Disclosures: Exelixis funded this study. The authors report no relevant financial disclosures.