Treatment Selection in Advanced MTC

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Frontline treatment selection for patients with advanced medullary thyroid cancer (MTC) who are not candidates for surgery can be traced back to the patients enrolled in the pivotal clinical trials that led to the approvals of cabozantinib and vandetanib, explains Marcia S. Brose, MD, PhD.

In the phase III ZETA trial that explored vandetanib, patients were not required to have progressive disease. However, the phase III EXAM trial focused on patients with progressive MTC. As a result, Brose generally considers cabozantinib as a preferred frontline therapy for patients with progressive MTC who require a rapid response.

Comparing the placebo arms between the two trials reveals the differences in the patient populations. In the ZETA trial, the median progression-free survival (PFS) with vandetanib was 30.5 months compared with 19.3 months with placebo (HR = 0.46; P <.001). In the EXAM trial, the median PFS was 11.2 months with cabozantinib compared with 4.0 months in the placebo arm (HR=0.28; P < .0001).

In addition to the efficacy seen in clinical trials, side effects can also be utilized for treatment selection. Patients with tracheal invasion or esophagus involvement should not receive cabozantinib, since it has been associated with fistulas, notes Brose. In this situation, vandetanib should be administered in the frontline setting. Additionally, a clinical trial might also represent a reasonable choice, Brose adds.

Both the TKIs for patients with MTC were approved with boxed warnings, notes Naifa L. Busaidy, MD. Cabozantinib carries a boxed warning for fatal bleeding, perforations, and fistulas. Vandetanib was approved with a warning regarding QT prolongation.

Each of these warnings should be considered in a multidisciplinary environment when treating patients, Busaidy notes. The risk of fistula formation with cabozantinib warrants the early involvement of a surgeon, endocrinologist, radiation, and medical oncologist. Additionally, hand-foot fatigue and diarrhea are common with cabozantinib, Busaidy adds.

VEGF inhibitors as a class have been connected with catabolic side effects, warranting upfront management to prevent muscle wasting, asthenia, and decreased appetite. To address these side effects, a dietician should be consulted, suggests Francis P. Worden, MD. Additionally, exercise programs that involve weight training can effectively control weight loss and even diarrhea, explains Brose. Exercise plans have produced impressive results, even in elderly patients.