FDA Ends REMS Program for Vandetanib in Medullary Thyroid Cancer

No cases of Torsades de pointes or unexplained sudden deaths occurred in patients in the United States receiving vandetanib.

The FDA has terminated its Risk Evaluation and Mitigation Strategies (REMS) program for vandetanib (Caprelsa), a drug whose use in patients with medullary thyroid cancer whose disease has spread or cannot be surgically removed has been approved since 2011.¹

Vandetanib is an oral TKI that has activity against multiple targets, including the EGFR family, the VEGFR family, RET, BRK, TIE2, members of the EPH receptor kinase family, and members of the Src kinase family.²

The agent was originally FDA approved with a REMS requirement due to the risk of QT prolongation and potentially fatal arrhythmias, including Torsades de pointes. However, following more than a decade of postmarketing oversight, REMS assessments reported no cases of Torsades de pointes or unexplained sudden deaths among patients in the United States who were treated with vandetanib.¹ Clinical data similarly revealed no concerning safety signals or consistent patterns of heart rhythm abnormalities, according to a news release. Based on these findings, the FDA determined that the REMS program is no longer necessary to ensure the safe use of vandetanib.

“Cancer specialists now have adequate knowledge about managing the heart rhythm–related risks of this medication,” Richard Pazdur, MD, director of the FDA Oncology Center of Excellence, noted in the news release. “Health care providers have incorporated proper safety monitoring into their standard practice, making the formal requirements unnecessary. The mandatory monitoring program has achieved its goals.”

With the removal of the REMS program, vandetanib will continue to be available under its current prescribing information; however, oncologists will no longer be required to obtain special certification or follow additional REMS-specific monitoring requirements beyond routine clinical practice.

What Were the Findings of the Retrospective Review of Vandetanib in Medullary Thyroid Cancer?

In February 2021, a retrospective review of clinical records from 76 patients with medullary thyroid cancer who were treated with vandetanib demonstrated that a substantial proportion of those who received first- or second-line therapy with the agent achieved sustained clinical benefit.³ Younger age at the time of diagnosis and the absence of confirmed disease progression prior to initiating treatment with vandetanib were identified as potential predictors of a durable response, suggesting that patients who begin therapy earlier in the disease course and without evidence of progression may derive prolonged clinical benefit.

In the retrospective review, among all patients with medullary thyroid cancer treated with vandetanib, the median progression-free survival (PFS) was 22.7 months (standard deviation [SD], 34.7), the complete response (CR) rate was 3.9%, the partial response (PR) rate was 36.8%), the stable disease rate was 43.4%, and the progressive disease (PD) rate was 3.9%. A total of 21 patients were classified as long-term users, defined as those who received vandetanib for more than 48 months. Among these long-term users, the median PFS was 73.2 months (SD, 29.0), and the rates of CR, PR, stable disease, and PD were 14.3%, 71.4%, 14.3%, and 0%, respectively. Among non–long-term users (n = 55), the median PFS was 13.4 months (SD, 18.4), and the rates of CR, PR, stable disease, and PD were 0%, 23.6%, 54.5%, and 5.5%, respectively. Furthermore, duration of response was negatively correlated with younger age at diagnosis and was significantly longer in patients without confirmed tumor progression prior to treatment initiation.

With regards to safety, following 48 months of treatment with vandetanib, renal failure was reported in a low number of patients. In addition, cases of heart failure, cholecystitis, acute pancreatitis, posterior encephalopathy, and skin cancer were observed.

References

1. FDA removes risk evaluation and mitigation strategies (REMS) for Caprelsa (vandetanib). FDA. September 25, 2025. Accessed September 25, 2025. https://www.fda.gov/news-events/press-announcements/fda-removes-risk-evaluation-and-mitigation-strategies-rems-caprelsa-vandetanib?utm_medium=email&utm_source=govdelivery
2. Caprelsa. Prescribing Information. Sanofi; May 2025. Accessed September 25, 2025. https://products.sanofi.us/caprelsa/caprelsa.pdf
3. Ramos HE, Hecht F, Berdelou A, et al. Long-term follow-up and safety of vandetanib for advanced medullary thyroid cancer. Endocrine. 2021;71(2):434-442. doi:10.1007/s12020-020-02426-x