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  • Title: Real-World Efficacy and Safety of Cabozantinib and Vandetanib in Advanced Medullary Thyroid Cancer.
    Author: Koehler VF, Adam P, Frank-Raue K, Raue F, Berg E, Hoster E, Allelein S, Schott M, Kroiss M, Spitzweg C.
    Journal: Thyroid; 2021 Mar; 31(3):459-469. PubMed ID: 32781914.
    Abstract:
    Background: Management of patients with advanced medullary thyroid cancer (MTC) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) vandetanib and cabozantinib have been approved for the treatment of progressive MTC based on prolonged progression-free survival (PFS) in phase 3 clinical trials. Patients and Methods: To evaluate clinical characteristics, treatment regimens, efficacy, and treatment emergent adverse events (TEAEs) of vandetanib and cabozantinib in MTC patients outside clinical trials at four German tertiary care centers. Forty-eight patients diagnosed between 1990 and 2018 were included. PFS and overall survival (OS) probabilities were estimated using the Kaplan-Meier method and compared by log-rank test. Results: The median age at diagnosis was 46 years (15-80 years); a germ line RET (rearranged during transfection) mutation was known in 6 (13%) patients. Thirty-two (67%) patients showed progressive disease before TKI initiation. Forty-seven (98%) patients were treated with vandetanib and 23 (48%) patients with cabozantinib. Vandetanib was first-line treatment in 41 (85%) patients and cabozantinib in 7 (15%) patients. Partial response was the best response in 12 (26%) patients treated with vandetanib and in 5 (22%) patients treated with cabozantinib. Sixteen (34%) patients treated with vandetanib and 3 (13%) patients treated with cabozantinib had stable disease ≥24 weeks. The median PFS for vandetanib and cabozantinib was 17 months [95% confidence interval, CI, 9.3-24.6 months] and 4 months [CI 3.1-4.9 months], respectively. The 6- and 12-month survival rates were 98% and 86% for vandetanib and 78% and 70% for cabozantinib, respectively. The median OS for vandetanib and cabozantinib was 53 months [CI 43.7-62.3 months] and 24 months [CI 5.9-42.1 months], respectively. In vandetanib-treated patients, the PFS and OS were significantly longer in patients aged ≤60 years at TKI initiation and in patients with ≥5 TEAEs. Additionally, the PFS was longer in the absence of bone metastases. In cabozantinib-treated patients, the PFS was significantly longer in patients experiencing TEAEs and in patients aged ≤60 years, and the OS was significantly longer in patients who had TEAEs and in patients with ≥5 TEAEs. Conclusions: Vandetanib and cabozantinib are effective treatment options in the majority of MTC patients. We hypothesize that the poorer prognosis of cabozantinib-treated patients in our retrospective analysis is most likely due to its use as second-line treatment after treatment failure on vandetanib. However, different degrees of efficacy of the two drugs are possible.
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