The FDA has removed the Risk Evaluation and Mitigation Strategies (REMS) program for vandetanib (Caprelsa), eliminating mandatory safety monitoring requirements for the medullary thyroid cancer treatment after more than a decade of postmarketing oversight demonstrated its safe use profile.
Vandetanib, an oral tyrosine kinase inhibitor approved in 2011 for patients with medullary thyroid cancer whose disease has spread or cannot be surgically removed, was originally subject to REMS requirements due to the risk of QT prolongation and potentially fatal arrhythmias, including Torsades de pointes.
Safety Profile Supports REMS Removal
Following more than ten years of postmarketing surveillance, REMS assessments reported no cases of Torsades de pointes or unexplained sudden deaths among patients in the United States who were treated with vandetanib. Clinical data similarly revealed no concerning safety signals or consistent patterns of heart rhythm abnormalities.
"Cancer specialists now have adequate knowledge about managing the heart rhythm–related risks of this medication," said Richard Pazdur, MD, director of the FDA Oncology Center of Excellence. "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."
Clinical Efficacy Data
A retrospective review published in February 2021 analyzed clinical records from 76 patients with medullary thyroid cancer treated with vandetanib, demonstrating that a substantial proportion of those who received first- or second-line therapy achieved sustained clinical benefit.
Among all patients treated with vandetanib, the median progression-free survival was 22.7 months (standard deviation 34.7), with a complete response rate of 3.9%, partial response rate of 36.8%, stable disease rate of 43.4%, and progressive disease rate of 3.9%.
Long-Term Treatment Outcomes
The study identified 21 patients as long-term users, defined as those who received vandetanib for more than 48 months. Among these patients, the median progression-free survival reached 73.2 months (SD 29.0), with response rates of 14.3% complete response, 71.4% partial response, 14.3% stable disease, and 0% progressive disease.
In contrast, non-long-term users (n=55) achieved a median progression-free survival of 13.4 months (SD 18.4), with response rates of 0% complete response, 23.6% partial response, 54.5% stable disease, and 5.5% progressive disease.
The analysis revealed that younger age at diagnosis and absence of confirmed disease progression prior to initiating vandetanib treatment were potential predictors of durable response, suggesting patients who begin therapy earlier in the disease course may derive prolonged clinical benefit.
Mechanism of Action
Vandetanib is an oral tyrosine kinase inhibitor with activity against multiple targets, including the EGFR family, VEGFR family, RET, BRK, TIE2, members of the EPH receptor kinase family, and members of the Src kinase family.
Safety Considerations
The long-term safety analysis showed that after 48 months of treatment, renal failure was reported in two patients, while heart failure, cholecystitis, acute pancreatitis, posterior encephalopathy, and skin cancer were each reported in one patient.
With the removal of the REMS program, vandetanib will continue to be available under its current prescribing information, but oncologists will no longer be required to obtain special certification or follow additional REMS-specific monitoring requirements beyond routine clinical practice.
