About the COSMIC-311 Trial of Cabozantinib in RAI-Refractory DTC

Francis P. Worden, MD, professor of medicine at the University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, provides background on the COSMIC-311 study (NCT03690388), highlighting the methods and design utilized.

COSMIC-311 is a phase 3 trial which enrolled patients aged 16 years old and older with radioiodine-refractory differentiated thyroid cancer who progressed on prior lenvatinib (Lenvima) and/or sorafenib (Nexavar). Patients were randomly assigned 2:1 to receive either oral cabozantinib (Cabometyx) tablets at a dose of 60 mg/day or a placebo.

Investigators evaluated the primary end points of objective response rate and progression-free survival in the intent-to-treat population according to RECIST v1.1 by blinded, independent review.

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0:10 | The COSMIC-311 study was a study that was conducted in patients in the second-line, so patients who had failed [tyrosine kinase inhibitor] therapy, primarily sorafenib or lenvatinib. They were randomized to cabometyx [cabozantinib], which is different from Cometriq, so the formulations are different. The salt is a little different, and it is 60 mg. Just a little bit about that, the old formulation of cabozantinib or Cometriq, which is the trade name used in medullary thyroid cancer, is kind of a difficult drug to tolerate. When the companies were thinking about redesigning agents, this agent was developed.

1:06 | Essentially, it's about half the dose, but a different formulation. There is a study in thyroid cancer, but other cancers that show Cabometyx are a little bit better tolerated than Cometriq. Nonetheless, Cometriq was compared with placebo in patients who were progressing on first-line therapy.

1:30 | The patients were randomized 2:1 to the drug vs placebo, and the response rates were somewhere around 13% for those receiving the cabozantinib vs 0% response rates in those who were receiving placebo. The primary end point was a dual end point, so they looked at response as well as improvement in progression-free survival.