Real-World Study Shows Vandetanib and Cabozantinib Effective for Advanced MTC

According to a real-world study, vandetanib and cabozantinib proved to be an effective first-line treatment in patients with advanced medullary thyroid cancer (MTC; Thyroid. 2020 Sep 23. Epub ahead of print). 

“Management of patients with advanced medullary thyroid cancer 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,” explained Viktoria F Koehler, Department of Internal Medicine IV, University Hospital, LMU Munich, Germany, and colleagues.

Koehler and her team conducted their research by evaluating clinical characteristics, treatment regimens, efficacy, and treatment-emergent adverse events (TEAEs) of vandetanib and cabozantinib in MTC patients across four German tertiary care centers. All 48 patients included in this study were diagnosed between 1990 and 2018 and evaluated outside of a clinical trial setting. 

The Kaplan-Meier method was implemented and compared by log-rank test to estimate PFS and overall survival (OS) probabilities. 

Of the 48 patients included, six had a germline RET (rearranged during transfection) mutation, and 32 showed progress disease before TKI initiation. 47 (98%) patients were treated with vandetanib, with 41 (85%) receiving it as first-line treatment. Alternatively, cabozantinib was given to 23 (48%) patients, with only seven receiving it as first-line treatment. 
 
At ≥24 weeks, stable disease occurred in 16 vandetanib patients and three cabozantinib patients, with the median PFS for vandetanib and cabozantinib being 17 (95% confidence interval, CI, 9.3-24.6 months) and four months (CI 3.1-4.9 months), respectively. The median OS  for both groups was 53 months (CI 43.7-62.3 months) and 23 months (CI 5.9-42.1 months), respectively. Furthermore, partial response was the best response in 12 (26%) vandetanib patients and 5 (22%) cabozantinib patients.

In the vandetanib group, the survival rate was 98% at 6 months and 86% at 12 months, while the 6-month and 12-month survival rate in the cabozantinib group was 78% and 70%, respectively. 

Patients who were under 60 years of age at the time of treatment experienced a significantly longer PFS and OS, as did those with  ≥5 TEAEs. The absence of bone metastases was also linked to a longer PFS. 

“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,” concluded Dr Koehler et al.—Alexandra Graziano