# EXAM

Source: https://onco.cc/trials/exam/  
OnCo record `exam` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-17
- Tags: subtype-trials
- Registry id: NCT00704730
- Phase: 3
- Setting: Progressive metastatic medullary thyroid cancer: cabozantinib against placebo
- Sponsor: Exelixis
- Enrolled: 330
- Result: Cabozantinib lengthened progression-free survival compared with placebo in progressive medullary thyroid cancer; approved in November 2012.
- Outcomes: Progression-free survival: Cabozantinib 140 mg 11.2 months vs Placebo 4 months, HR 0.28; Objective response rate: Cabozantinib 140 mg 28% vs Placebo 0%; Alive and progression-free at 1 year: Cabozantinib 140 mg 47.3% vs Placebo 7.2%

## Sources

- ClinicalTrials.gov NCT00704730: https://clinicaltrials.gov/study/NCT00704730

## Connected records

- cancers: [Medullary thyroid cancer](https://onco.cc/cancers/medullary-thyroid-cancer/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Cabozantinib](https://onco.cc/drugs/cabozantinib/)
- companies: [Exelixis](https://onco.cc/companies/exelixis/)
- people: [Rossella Elisei](https://onco.cc/people/rossella-elisei/)
- key papers: [EXAM: cabozantinib in progressive medullary thyroid cancer](https://onco.cc/key-papers/paper-exam-cabozantinib-mtc-elisei-jco-2013/)

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