Francis P. Worden, MD, provides background on the COSMIC-311 study, highlighting the methods and design utilized.
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.
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.