EXAM: cabozantinib in progressive medullary thyroid cancer
Cabozantinib, a kinase inhibitor blocking RET, MET and VEGF receptors, delayed progression by more than seven months compared with placebo in progressive medullary thyroid cancer, at the cost of considerable toxicity.
Overview
Phase 3 placebo-controlled trial of 330 patients with progressive metastatic medullary thyroid cancer randomised 2:1 to cabozantinib 140 mg daily or placebo.
Median progression-free survival was 11.2 versus 4.0 months (hazard ratio 0.28) and response 28 versus 0 percent, with benefit regardless of RET status; diarrhoea, hand-foot syndrome, weight loss and fistula were notable toxicities.
- Median progression-free survival 11.2 vs 4.0 months; hazard ratio 0.28.
- Objective response 28 percent vs 0 percent.
Cabozantinib is an option for progressive medullary thyroid cancer, now mainly for RET-negative disease or after selpercatinib.
- No overall survival benefit overall, though RET M918T carriers may have benefited.
- High dose with frequent reductions.
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