FDA Drops REMS Requirement for Vandetanib in Medullary Thyroid Cancer

The FDA has removed the Risk Evaluation and Mitigation Strategies (REMS) program for vandetanib (Caprelsa) intended to ensure appropriate heart rhythm monitoring and safe use in patients with medullary thyroid cancer, according to a release from the FDA.¹

Vandetanib was approved to treat medullary thyroid cancer in patients whose disease had spread or could not be removed via surgery by the FDA in April 2011.² The REMS program was implemented as a safeguard due to risks of QT prolongation, Torsades de pointes, and sudden death.

Following over a decade of oversight, no cases of Torsades de pointes or unexplained sudden deaths were reported among US patients who received vandetanib in REMS assessments. Clinical data also showed no concerning patterns of heart rhythm problems.

The prescribing information of vandetanib will not change, although health care providers will not require special certifications or extra monitoring beyond standard clinical care. To be certified for the REMS program, physicians were required to review several pamphlets, complete a set of training questions, and acknowledge that they would review the necessary information with each patient.

As is, the warning label warns not to use vandetanib in patients with hypocalcemia, hypokalemia, hypomagnesia, and long QT syndrome. All must be corrected prior to administration, and electrolytes are required to be monitored periodically.³

“Cancer specialists now have adequate knowledge about managing the heart rhythm-related risks of this medication,” stated Richard Pazdur, MD, the director of the FDA Oncology Center of Excellence, in the press release.¹ “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.”

In the 231 patients included in the experimental arm of the phase 3 ZETA clinical trial (NCT00410761)—the trial which supported vandetanib’s approval—300 mg of vandetanib once daily was associated with sustained plasma concentration-dependent QT prolongation, with 14% and 8% of patients experiencing all-grade and grade 3 or 4 , respectively, electrocardiogram QT prolongation.^4,5

Of the patients who received vandetanib, 69% had QT prolongation greater than 450 ms, and 7% had QT prolongation greater than 500 ms via electrocardiogram using Fridericia correction (QTcF).

The mean QTcF change from baseline was 35 ms (90% CI, 33-36) with the 300-mg dose; for up to 2 years, the mean QTcF change in baseline remained above 30 ms.

Notably, due to the 19-day half-life, adverse reactions, including prolonged QT interval, had the possibility of not resolving quickly.

In the trial, vandetanib achieved a median progression-free survival (PFS) of not reached (NR; 95% CI, 22.6-not evaluable [NE]) compared with 16.4 months (95% CI, 8.3-19.7) with placebo (HR, 0.35; 95% CI, 0.24-0.53; P <.001). The median overall survival was 81.6 months (95% CI, 64.6-98.5) vs 80.4 months (95% CI, 52.5-NE), respectively (HR, 0.99; 95% CI, 0.72-1.38; P = .975).

Furthermore, the objective response rate was 44% with vandetanib compared with 1% with placebo; all objective responses were partial responses.

The most common any-grade adverse reactions with vandetanib were diarrhea/colitis (57%), acneiform dermatitis (35%), rash (33%), nausea (33%), hypertension (33%), and headache (26%). The most common grade 3 or higher adverse reactions were diarrhea/colitis (11%), hypertension (9%), fatigue (6%), rash (5%), and abdominal pain (3%). Blurred vision also occurred in 9% of patients who received vandetanib.

Dose interruptions, dose reductions, and treatment discontinuation occurred in 47%, 36%, and 12% of patients who received vandetanib.

Other clinically important uncommon adverse reactions with vandetanib included pancreatitis (0.4%), intestinal perforation (0.4%), and heart failure (0.9%).

References

1. FDA removes risk evaluation and mitigation strategies (REMS) for Caprelsa (vandetanib). News release. FDA. September 25, 2025. Accessed September 25, 2025. https://tinyurl.com/ms9ewb3c
2. FDA approves orphan drug vandetanib. News release. AstraZeneca. April 7, 2011. Accessed September 26, 2025. https://tinyurl.com/4kyahr5h
3. Highlights of prescribing information. CAPRELSA® (vandetanib) tablets, for oral use. Sanofi. Accessed September 26, 2025. https://tinyurl.com/ytukt37h
4. Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30(2):134-141. doi:10.1200/JCO.2011.35.5040
5. CAPRELSA® (vandetanib) tablets and risk of QT prolongation, Torsades de Pointes and sudden death. Prescriber training pamphlet. Genzyme Corporation. Updated July 2016. Accessed September 26, 2025. https://tinyurl.com/4h84e52j