Cabozantinib significantly improved progression-free survival (PFS) in certain patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), according to results from the COSMIC-311 study. 

The COSMIC-311 trial tested cabozantinib  (Cabometyx, Exelixis) against placebo in patients with RAI-refractory DTC who had progressed after treatment with up to two vascular endothelial growth factor receptor inhibitors. To be enrolled, patients had to have an Eastern Cooperative Oncology Group status of 0 to 1 and to have been treated previously with lenvatinib (Lenvima, Eisai) or sorafenib (Nexavar, Bayer). Patients, stratified based on receipt of lenvatinib and age (≤65 vs. >65 years), were randomly assigned in a 2:1 fashion to receive cabozantinib at a dose of 60 mg daily (n=125) or placebo (n=62). The primary end points were response rate and PFS. After progression, patients on placebo were allowed to cross over to receive cabozantinib.

Presenting the findings at the annual meeting of the American Society of Clinical Oncology (abstract 6001), Marcia Brose, MD, PhD, from Abramson Cancer Center, in Philadelphia, reported that at the first planned interim analysis, at a median follow-up of 6.2 months, the primary end point for PFS was met with a hazard ratio of 0.22 (95% CI, 0.13-0.36; P<0.0001); at that point, the independent data review monitoring committee recommended that enrollment be stopped. The median PFS was not reached in the cabozantinib group and was 1.9 months in the placebo group. The benefit was seen across all subgroups. Response rate was 0 in the placebo arm and 15% in the cabozantinib arm, but three-fourths of the treatment group experienced some tumor shrinkage. 

In terms of tolerability, 62% of cabozantinib-treated patients required dose modification because of adverse events. Nearly half had an adverse event of grade 3 to 4. There were no deaths attributed to cabozantinib.

“We can conclude from this trial that cabozantinib has impressive activity in previously treated differentiated thyroid cancer. It’s likely to become the standard of care in this setting,” commented Danny Rishcin, MD, MBBS, the director of the Division of Cancer Medicine and head of the Department of Medical Oncology at Peter MacCallum Cancer Center, in Victoria, Australia, who discussed the study during an ASCO session on highlights of the day. “These results should not be extrapolated to poor?performance status patients in the wider community.” Dr. Rishcin pointed out that the overall survival analysis is immature, underpowered and confounded by crossover.

—Kate O’Rourke

Dr. Brose reported financial relationships with Bayer, Blueprint Medicines, Eisai, Exelixis, Lilly and Loxo. Dr. Rishcin reported financial relationships with GlaxoSmithKline and Merck.