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Cabozantinib Active in Advanced Thyroid Cancer

Cabozantinib Active in Advanced Thyroid Cancer

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Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Half of patients with radioactive iodine (RAI)-refractory thyroid cancer responded to treatment with the multikinase inhibitor cabozantinib (Cometriq).
  • Note that a review of adverse events (all grades) showed that hyperglycemia (80%), diarrhea (77%), malaise/fatigue (74%), and weight loss (71%) occurred most often but were mostly grade 1 and 2.

Half of patients with radioactive iodine (RAI)-refractory thyroid cancer responded to treatment with the multikinase inhibitor cabozantinib (Cometriq), initial results from an ongoing study showed.

The data showed that 19 of 35 patients had partial responses and another 15 had stable disease, including nine patients whose disease remained stable for more than 6 months. Median progression-free survival (PFS) had yet to be reached.

In many cases, responses were durable, said Marcia Brose, MD, of the University of Pennsylvania in Philadelphia, noting that enrollment in the study started more than 3 years ago, and some patients still had ongoing responses.

“This single-site phase II study showed that cabozantinib is an active agent for radioactive iodine-refractory differentiated thyroid cancer in the first-line setting,” Brose concluded a presentation during a press briefing prior to the Multidisciplinary Head and Neck Cancer Symposium. “Treatment with cabozantinib resulted in a 54% response rate and an 80% clinical benefit rate, meeting the primary endpoint of the study.”

Two tyrosine kinase inhibitors already have FDA approval for treatment of advanced thyroid cancer, and many patients achieve objective responses with the agents. However, most patients eventually progress, creating a need for additional effective therapies to offer such patients, said press briefing moderator Danielle Margalit, MD, of Dana-Farber Cancer Institute in Boston.

“These results are significant because they show that cabozantinib had good activity, with a 54% objective response rate in the first-line setting, which is comparable or superior to the recently approved agents,” said Margalit. “It’s also tolerable at the 60-milligram dose used in this study, which is different from the FDA-approved dose used for medullary thyroid carcinoma, 140 milligrams, which is often difficult to tolerate.”

Cabozantinib targets VEGF receptor tyrosine kinase, as well as RET, MET, and AXL. The drug previously received FDA approval for advanced medullary thyroid cancer and renal cell cancer.

Results of a phase I study suggested cabozantinib had activity in RAI-refractory differentiated thyroid cancer already treated with one or more prior therapies, including VEGF receptor inhibitors. Brose and colleagues continued investigation of cabozantinib in a phase II single-arm trial involving patients with newly diagnosed RAI-refractory differentiated thyroid cancer.

All patients received cabozantinib 60 mg daily, continued until disease progression or development of intolerable toxicity. The trial had a primary endpoint of overall response rate by RECIST criteria. Secondary endpoints included PFS, clinical benefit rate, and safety.

A response rate of 15%, or at least five responses (complete or partial) in the first 35 patients, was considered the minimum activity for consideration of cabozantinib for further investigation in RAI-refractory differentiated thyroid cancer, said Brose.

Median age for the 35 patients was 65. Tumor histology was papillary in two-thirds of cases, follicular in 9%, and poorly differentiated in 26%.

Response assessment showed that treatment led to partial responses in 19 patients. When the responding patients were combined with the nine patients who had stable disease for more than 6 months, the treatment resulted in a clinical benefit rate of 80% (28 out of 35 patients).

The patients remained in follow-up for determination of the primary endpoint, as only six of 35 patients had developed progressive disease. The median duration of treatment was 35 weeks. Brose said all but one patient had some degree of tumor shrinkage during treatment with cabozantinib, ranging from about 10% to as much as 70%.

A review of adverse events (all grades) showed that hyperglycemia (80%), diarrhea (77%), malaise/fatigue (74%), and weight loss (71%) occurred most often. Grade 3-5 adverse events affecting more than one patient consisted of hypertension in five (14%) patients, increased lipase in three (9%), pulmonary embolism in two (6%), and hyponatremia in two (6%).

“Cabozantinib was well tolerated, with mostly grade 1 and 2 adverse events,” said Brose. “No unexpected toxicities were identified. Cabozantinib is an active agent in these patients and merits additional study in a large multicenter phase III trial to determine its efficacy in patients with radioactive iodine-refractory differentiated thyroid cancer.”

The Multidisciplinary Head and Neck Cancer Symposium begins Thursday and continues through Saturday in Scottsdale, Arizona. The symposium is co-sponsored by the American Society for Radiation Oncology, the American Society of Clinical Oncology, and the American Head & Neck Society.

Brose reported relationships with Loxo, Exelixis, Bayer, Eisai, Sanofi, AstraZeneca, and Blueprint Pharmaceuticals.

  • Reviewed by
    Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

2018-02-13T16:45:32-0500

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