The US Food and Drug Administration (FDA) has approved cabozantinib (Cabometyx) for the treatment of locally advanced or metastatic differentiated thyroid cancer (DTC) in adults and children aged 12 years and older. Specifically, it is indicated for patients whose disease has progressed after they have received VEGFR-targeted therapy and who are ineligible for or whose condition is refractory to radioactive iodine therapy.
In the United States, cabozantinib is currently approved for the treatment of medullary thyroid cancer, renal cell carcinoma, and hepatocellular carcinoma.
DTC is the most common type of thyroid cancer in the United States. It accounts for about 90% of all thyroid cancer cases. It is typically treated with surgery followed by ablation of the remaining thyroid tissue with radioiodine, but 5% to 15% of cases are resistant to radioiodine treatment. For these patients, prognosis is poor; life expectancy averages only 3 to 5 years from the time metastatic lesions are detected.
“Before today, patients with radioactive iodine–refractory differentiated thyroid cancer who have progressed following prior VEGFR-targeted therapy were facing aggressive disease and no standard treatment option,” commented Marcia S. Brose, MD, PhD, from the Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, Pennsylvnia, in a company press release. She was principal investigator of the pivotal trial that led to approval of the new indication. That trial showed that “cabozantinib extended the time that patients live without progression of their cancer.”
“The FDA approval of cabozantinib is an important advancement for these patients who are badly in need of new treatment options,” she added.
Details of Updated Results
This latest approval is based on results from COSMIC-311, a phase 3 randomized, placebo-controlled trial that compared cabozantinib with placebo in patients with radioactive iodine–refractory DTC who experienced disease progression after receiving up to two prior VEGFR-targeted therapies. The cohort included 258 patients who were enrolled at 164 sites globally. Patients were randomly assigned in a 2:1 ratio to receive either cabozantinib 60 mg or placebo once daily.
In findings from a planned interim analysis, treatment with cabozantinib significantly reduced the risk for disease progression or death in comparison with placebo (P < .0001) in the intent-to-treat population.
The results of the final analysis were presented on September 20 at the European Society of Medical Oncology Congress.
Median progression-free survival was 11.0 months for patients in the treatment group (n = 170) and 1.9 months for patients treated with placebo (n = 88). Benefit was consistent in subgroups that were based on prior treatment.
An updated analysis for the primary endpoint of objective response rate also favored cabozantinib, at 11%, including one complete response, vs 0% for placebo. Median overall survival was 19.4 months for the cabozantinib group; it was not estimable for patients treated with placebo (hazard ratio, 0.76; 95% CI, 0.45 – 1.31).
The most common adverse events that were reported in at least 25% of patients treated with cabozantinib were diarrhea, palmar-plantar erythrodysesthesia, fatigue, hypertension, and stomatitis. Grade 3/4 adverse events that occurred in at least 5% of patients were palmar-plantar erythrodysesthesia, hypertension, fatigue, diarrhea, and stomatitis. Serious events that occurred in 34% of patients were diarrhea, pleural effusion, pulmonary embolism, and dyspnea. These were the most common adverse events and were reported in at least 2% of patients.
Fatal adverse events occurred in 1.6% of patients in the cabozantinib arm. These included arterial hemorrhage (0.8%) and pulmonary embolism (0.8%). Dose reductions were required in 56% of patients; 22% required a second dose reduction, and adverse events leading to drug discontinuation occurred in 5% of patients.
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