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EXAM showed that cabozantinib, which blocks RET, MET and VEGF receptors, held back progressive medullary thyroid cancer for far longer than placebo, and gave the disease its second approved targeted drug.
Medullary thyroid cancer arises from calcitonin-producing C cells and is driven by RET mutations in the hereditary and about half of sporadic cases. EXAM randomised 330 patients with documented progressive metastatic medullary thyroid cancer two to one to cabozantinib 140 mg daily or placebo, with progression-free survival as the primary endpoint.
Cabozantinib lengthened progression-free survival several-fold and produced objective responses in a substantial minority, regardless of RET mutation status, at the cost of diarrhoea, hand-foot syndrome, fatigue and hypertension. Overall survival was not significantly different in the whole population. It was approved in the United States in November 2012, following vandetanib (ZETA) as the second multikinase inhibitor for the disease; the selective RET inhibitors selpercatinib and pralsetinib have since displaced both for RET-mutant tumours.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
330 enrolled.
Shares Exelixis, Cabozantinib, Anti-angiogenic therapy, Small-molecule kinase inhibitors and the tag subtype-trials.
Shares Exelixis, Cabozantinib, Anti-angiogenic therapy, Small-molecule kinase inhibitors and the tag subtype-trials.
Shares Medullary thyroid cancer, Thyroid cancer, Small-molecule kinase inhibitors and the tag subtype-trials.
Shares Anti-angiogenic therapy, Small-molecule kinase inhibitors and the tag subtype-trials.
Shares Anti-angiogenic therapy, Small-molecule kinase inhibitors and the tag subtype-trials.
Shares Anti-angiogenic therapy, Small-molecule kinase inhibitors and the tag subtype-trials.
Shares Anti-angiogenic therapy and the tag subtype-trials.
Shares Anti-angiogenic therapy and the tag subtype-trials.