FDA Approves Second Drug for Rare Thyroid Cancer

Cabozantinib, a kinase inhibitor, has been approved for the treatment of progressive, metastatic medullary thyroid cancer, on the basis of the results of an international study of 330 patients, the Food and Drug Administration has announced.

This is the second drug approved by the FDA for this indication in the past 2 years; the first was vandetanib (Caprelsa), approved in April 2011. Before these approvals, "patients with this rare and difficult to treat disease had limited therapeutic treatment options," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s Nov. 29 statement announcing the approval.

Cabozantinib will be marketed as Cometriq by Exelixis Inc. The recommended dose is 140 mg orally, without food (people taking the drug should not eat for at least 2 hours before and at least 1 hour after taking it). Exelixis is planning to make the drug available in late January, at an average wholesale price of $9,900 for a 28-day supply, according to the company.

In the EXAM study of 330 patients with metastatic medullary thyroid cancer, with evidence of actively progressive disease within 14 months of enrollment, the median progression-free survival was 11.2 months among those treated with cabozantinib, compared with 4 months among those on placebo, a statistically significant difference, according to the prescribing information. Partial responses were observed among 27% of those on cabozantinib but none of those on placebo, and the median duration of the objective response was 14.7 months among those on cabozantinib. At the planned interim analysis, there was no statistically significant difference in overall survival between the two groups.

The most common adverse events, reported in at least 25% of patients treated with cabozantinib, were diarrhea; stomatitis, palmar-plantar erythrodysesthesia syndrome; decreases in weight and appetite; nausea; fatigue; oral pain; hair color changes; dysgeusia; hypertension; abdominal pain; and constipation. The most common laboratory abnormalities, reported in at least 25% of patients, were increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The prescribing information includes a boxed warning about severe and sometimes fatal hemorrhage (3%), and gastrointestinal perforations (3%) and fistulas (1%) were reported in patients treated with the drug.

The review of this drug was a priority review, completed in 6 months, which is used for drugs "that may offer major advances in treatment or that provide a treatment when no adequate therapy exists," the FDA statement said. The drug has also been designated an orphan drug, because medullary thyroid cancer is considered a rare disease.

As part of its postmarketing commitments, the FDA has requested that the company submit the final overall survival results of the study, expected to be submitted in December 2014, according to the agency’s approval letter. The letter also lists other postmarketing commitments, including the completion of a study comparing the approved dose of "a biologically active and potentially safer lower daily cabozantinib dose" in patients with progressive medullary thyroid cancer.

Cabozantinib is a kinase inhibitor that inhibits the activity of RET, MET, and other tyrosine kinases, which "are involved in both normal cellular function, and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment," according to the Exelixis statement announcing approval

The company also announced on Nov. 29 that the application for approval of cabozantinib, also based on the EXAM study, has been accepted by the European Medicines Agency for approval in the European Union.

The FDA statement cites estimates from the National Cancer Institute that 56,460 people will be diagnosed with thyroid cancer this year in the United States, and 1,780 will die from the disease, and about 4% percent of thyroid cancers are medullary thyroid cancer.

The drug’s label is available on the FDA website. Serious adverse events associated with the drug should be reported to the FDA’s MedWatch site or at 800-332-1088.

Cabozantinib, a kinase inhibitor, has been approved for the treatment of progressive, metastatic medullary thyroid cancer, on the basis of the results of an international study of 330 patients, the Food and Drug Administration has announced.

This is the second drug approved by the FDA for this indication in the past 2 years; the first was vandetanib (Caprelsa), approved in April 2011. Before these approvals, "patients with this rare and difficult to treat disease had limited therapeutic treatment options," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s Nov. 29 statement announcing the approval.

Cabozantinib will be marketed as Cometriq by Exelixis Inc. The recommended dose is 140 mg orally, without food (people taking the drug should not eat for at least 2 hours before and at least 1 hour after taking it). Exelixis is planning to make the drug available in late January, at an average wholesale price of $9,900 for a 28-day supply, according to the company.

In the EXAM study of 330 patients with metastatic medullary thyroid cancer, with evidence of actively progressive disease within 14 months of enrollment, the median progression-free survival was 11.2 months among those treated with cabozantinib, compared with 4 months among those on placebo, a statistically significant difference, according to the prescribing information. Partial responses were observed among 27% of those on cabozantinib but none of those on placebo, and the median duration of the objective response was 14.7 months among those on cabozantinib. At the planned interim analysis, there was no statistically significant difference in overall survival between the two groups.

The most common adverse events, reported in at least 25% of patients treated with cabozantinib, were diarrhea; stomatitis, palmar-plantar erythrodysesthesia syndrome; decreases in weight and appetite; nausea; fatigue; oral pain; hair color changes; dysgeusia; hypertension; abdominal pain; and constipation. The most common laboratory abnormalities, reported in at least 25% of patients, were increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The prescribing information includes a boxed warning about severe and sometimes fatal hemorrhage (3%), and gastrointestinal perforations (3%) and fistulas (1%) were reported in patients treated with the drug.

The review of this drug was a priority review, completed in 6 months, which is used for drugs "that may offer major advances in treatment or that provide a treatment when no adequate therapy exists," the FDA statement said. The drug has also been designated an orphan drug, because medullary thyroid cancer is considered a rare disease.

As part of its postmarketing commitments, the FDA has requested that the company submit the final overall survival results of the study, expected to be submitted in December 2014, according to the agency’s approval letter. The letter also lists other postmarketing commitments, including the completion of a study comparing the approved dose of "a biologically active and potentially safer lower daily cabozantinib dose" in patients with progressive medullary thyroid cancer.

Cabozantinib is a kinase inhibitor that inhibits the activity of RET, MET, and other tyrosine kinases, which "are involved in both normal cellular function, and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment," according to the Exelixis statement announcing approval

The company also announced on Nov. 29 that the application for approval of cabozantinib, also based on the EXAM study, has been accepted by the European Medicines Agency for approval in the European Union.

The FDA statement cites estimates from the National Cancer Institute that 56,460 people will be diagnosed with thyroid cancer this year in the United States, and 1,780 will die from the disease, and about 4% percent of thyroid cancers are medullary thyroid cancer.

The drug’s label is available on the FDA website. Serious adverse events associated with the drug should be reported to the FDA’s MedWatch site or at 800-332-1088.

Cabozantinib, a kinase inhibitor, has been approved for the treatment of progressive, metastatic medullary thyroid cancer, on the basis of the results of an international study of 330 patients, the Food and Drug Administration has announced.

This is the second drug approved by the FDA for this indication in the past 2 years; the first was vandetanib (Caprelsa), approved in April 2011. Before these approvals, "patients with this rare and difficult to treat disease had limited therapeutic treatment options," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s Nov. 29 statement announcing the approval.

Cabozantinib will be marketed as Cometriq by Exelixis Inc. The recommended dose is 140 mg orally, without food (people taking the drug should not eat for at least 2 hours before and at least 1 hour after taking it). Exelixis is planning to make the drug available in late January, at an average wholesale price of $9,900 for a 28-day supply, according to the company.

In the EXAM study of 330 patients with metastatic medullary thyroid cancer, with evidence of actively progressive disease within 14 months of enrollment, the median progression-free survival was 11.2 months among those treated with cabozantinib, compared with 4 months among those on placebo, a statistically significant difference, according to the prescribing information. Partial responses were observed among 27% of those on cabozantinib but none of those on placebo, and the median duration of the objective response was 14.7 months among those on cabozantinib. At the planned interim analysis, there was no statistically significant difference in overall survival between the two groups.

The most common adverse events, reported in at least 25% of patients treated with cabozantinib, were diarrhea; stomatitis, palmar-plantar erythrodysesthesia syndrome; decreases in weight and appetite; nausea; fatigue; oral pain; hair color changes; dysgeusia; hypertension; abdominal pain; and constipation. The most common laboratory abnormalities, reported in at least 25% of patients, were increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The prescribing information includes a boxed warning about severe and sometimes fatal hemorrhage (3%), and gastrointestinal perforations (3%) and fistulas (1%) were reported in patients treated with the drug.

The review of this drug was a priority review, completed in 6 months, which is used for drugs "that may offer major advances in treatment or that provide a treatment when no adequate therapy exists," the FDA statement said. The drug has also been designated an orphan drug, because medullary thyroid cancer is considered a rare disease.

As part of its postmarketing commitments, the FDA has requested that the company submit the final overall survival results of the study, expected to be submitted in December 2014, according to the agency’s approval letter. The letter also lists other postmarketing commitments, including the completion of a study comparing the approved dose of "a biologically active and potentially safer lower daily cabozantinib dose" in patients with progressive medullary thyroid cancer.

Cabozantinib is a kinase inhibitor that inhibits the activity of RET, MET, and other tyrosine kinases, which "are involved in both normal cellular function, and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment," according to the Exelixis statement announcing approval

The company also announced on Nov. 29 that the application for approval of cabozantinib, also based on the EXAM study, has been accepted by the European Medicines Agency for approval in the European Union.

The FDA statement cites estimates from the National Cancer Institute that 56,460 people will be diagnosed with thyroid cancer this year in the United States, and 1,780 will die from the disease, and about 4% percent of thyroid cancers are medullary thyroid cancer.

The drug’s label is available on the FDA website. Serious adverse events associated with the drug should be reported to the FDA’s MedWatch site or at 800-332-1088.