Safety/Efficacy Findings Support Cabozantinib in RAI-Refractory DTC

Francis P. Worden, MD, professor of medicine at the University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, reviews the progression-free survival (PFS) data and safety findings from the phase 3 COSMIC-311 study (NCT03690388) which evaluated treatment with cabozantinib (Cabometyx) in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC).

In the study, patients aged 16 years and older with RAIR-DTC were randomly assigned in a 2:1 ratio to receive oral cabozantinib tablets at a dose of 60 mg/day or a placebo. Investigators evaluated the primary end points of objective response rate and PFS in the intent-to-treat population, according to RECIST v1.1 by blinded, independent review.

According to safety findings, grade 3/4 treatment-emergent adverse events (AEs) were seen in 62% of patients given cabozantinib compared with 28% given placebo. With cabozantinib vs placebo, the most common AEs observed were hypertension (12% v 2%), palmar-plantar erythrodysesthesia (10% v 0%), and fatigue (9% v 0%). There were no grade 5 treatment-related AEs observed in the study and no new safety signals.

Further, extended follow-up showed that patients treated with cabozantinib also had better efficacy results vs patients treated with placebo. Overall, the findings from the phase 3 COSMIC-311 study support treatment with cabozantinib for this patient population.

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0:10 | If we look at the data, the median progression-free survival with prior lenvatinib was 5.8 months vs 16.6 months with sorafenib. But overall, again, we see the total improvement when the 2 drugs are combined together.

0:30 | Tolerability is similar to what we see with the other multi-targeted kinase inhibitors. Hypertension and hand-foot syndrome can be an issue, as we know with cabozantinib, as well as general fatigue. Overall, for second-line therapy, patients did quite well with this agent, and it should be considered once people fail first-line therapy with lenvatinib.