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Real world efficacy and safety of cabozantinib and vandetanib in advanced medullary thyroid cancer.

BACKGROUND
Management of patients with advanced medullary thyroid carcinoma (MTC) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKI) 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 (TEAE) of vandetanib and cabozantinib in MTC-patients outside of 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
Median age at diagnosis was 46 (15-80) years, a germ line RET-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, 23 (48%) with cabozantinib. Vandetanib was the first line treatment in 41 (85%) patients and cabozantinib in 7 (15%). Partial response was the best response in 12 (26%) vandetanib patients and in 5 (22%) cabozantinib patients. Stable disease ≥ 24 weeks was detected in 16 (34%) vandetanib patients and in 3 (13%) cabozantinib patients. Median PFS for vandetanib and cabozantinib were 17 (95% confidence interval, 9.3-24.6) and 4 (95% CI, 3.1-4.9) months. The 6- and 12-month survival rates were 98% and 86% for vandetanib and 78% and 70% for cabozantinib. Median OS for vandetanib and cabozantinib were 53 (95% CI, 43.7-62.3) and 24 (95% CI, 5.9-42.1) months. In vandetanib-treated patients PFS and OS were significantly longer in patients ≤ 60 years at TKI-initiation and patients with ≥ 5 TEAEs, additionally PFS was longer in the absence of bone metastases. In cabozantinib-treated patients PFS was significantly longer in patients experiencing TEAEs and patients ≤ 60 years, OS was significantly longer in patients having TEAEs and in patients with ≥ 5 TEAEs.


CONCLUSION
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.