Related Experiment Video
Updated: Mar 30, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer
Jolanta Krajewska1, Tomasz Olczyk1, Barbara Jarzab1
1a Nuclear Medicine and Endocrine Oncology Department , M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology , Gliwice , Poland.
Abstract:
Cabozantinib (XL-184) is a potent inhibitor of MET, VEGFR 2/KDR, RET and other receptor tyrosine kinases, such as KIT, AXL and FLT3. Its efficacy against MTC has been demonstrated in a prospective, randomized, placebo-controlled study (EXAM). Cabozantinib comparing to placebo significantly prolonged progression free survival both in hereditary and sporadic MTC, 11.2 vs 4.0 months, respectively. Final analysis showed no global differences in overall survival (OS) between cabozantinib and placebo. However, in a subgroup with RET M918T mutation the difference in OS was significant: 44.3 vs 18.9 months, respectively. Among the most frequent cabozantinib-related adverse events (AEs), observed in >30% of patients were diarrhea, palmar-plantar erythrodysesthesia, decreased weight, decreased appetite, nausea, fatigue, dysgeusia, hair color changes and hypertension. Expert Commentary: Cabozantinib constitutes an effective treatment option with acceptable toxicity in MTC patients showing either germinal or sporadic tumor RET M918T mutation as the drug prolonged OS in these subjects.
Insights
Cabozantinib significantly improved progression-free survival in medullary thyroid cancer (MTC). In patients with the RET M918T mutation, cabozantinib also demonstrated a significant overall survival benefit.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Medullary thyroid cancer (MTC) is a rare endocrine malignancy.
- Cabozantinib is a multi-targeted tyrosine kinase inhibitor (TKI).
- The RET M918T mutation is a key driver in some MTCs.
Purpose of the Study:
- To evaluate the efficacy and safety of cabozantinib in MTC patients.
- To assess the impact of cabozantinib on progression-free survival (PFS) and overall survival (OS).
- To investigate outcomes in relation to the RET M918T mutation status.
Main Methods:
- A prospective, randomized, placebo-controlled trial (EXAM study).
- Patients with hereditary or sporadic MTC were included.
- Treatment arms compared cabozantinib versus placebo.
Main Results:
- Cabozantinib significantly prolonged PFS compared to placebo (11.2 vs 4.0 months).
- No significant difference in global OS was observed.
- A significant OS benefit was seen in the subgroup with the RET M918T mutation (44.3 vs 18.9 months).
- Common adverse events included diarrhea, palmar-plantar erythrodysesthesia, and fatigue.
Conclusions:
- Cabozantinib is an effective treatment for MTC, improving PFS.
- Cabozantinib offers a significant OS advantage in MTC patients with the RET M918T mutation.
- The drug presents an acceptable toxicity profile for this patient population.
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