Jochen H. Lorch, MD, MS
Though some patients with medullary thyroid cancer (MTC) can live with their disease without progression for long periods of time, the majority will eventually enter a phase in which their cancer becomes much more aggressive, according to Jochen H. Lorch, MD, MS.
"At this point, we don’t really know what prompts cancers to enter the accelerated phase," said Lorch, assistant professor of medicine at Harvard Medical School and director of the Thyroid Cancer Center at Dana-Farber Cancer Institute. "There must be some additional genetic event that occurs."
At present, there are 2 FDA-approved treatments for patients with MTC after progression. However, these therapies are not well tolerated, and neither provides a cure, according to Lorch.
In an interview with OncLive
at the 2016 American Thyroid Association annual meeting, Lorch discussed current approved treatment options for patients with MTC, the biology of the disease, management of potential progression, and future possibilities in this treatment landscape.
OncLive: What is the standard treatment for MTC?
: MTC is a rare disease among endocrine cancers; [it makes up] less than 4% of all thyroid cancers. Many times, MTC is stable and does not require treatment for many years. Eventually, though, most patients enter an accelerated phase where they do require systemic treatment.
There are currently 2 FDA-approved drugs for cases where the cancer progresses beyond the initial treatment of surgery or surveillance—vandetanib (Caprelsa) and cabozantinib (Cometriq). Both were based on phase III data. These were randomized trials, similar in size; however, the entry criteria were quite different. In the vandetanib trial, for example, there was no explicit requirement for disease progression. While in the cabozantinib study, progression was required for a little more than a year. Both trials showed a difference in progression-free survival (PFS). There was, however, no difference in overall survival, due to crossover.
Subset analyses in the cabozantinib trial identified a subset of patients with a specific mutation in the RET
proto-oncogene, the M918T
mutation, which is typically associated with aggressive growth and a poor prognosis. Those patients actually had a survival benefit.
How do you determine which drug to give each patient?
The big question is what are you going to use first among these 2 drugs, and there is really no clear guide. Those 2 randomized trials were designed in quite different ways so you can’t directly compare the results. On the surface, vandetanib had much longer PFS than cabozantinib. However, the placebo arm in this trial also had PFS of a year and a half, which means that patients who received the placebo still had disease stability for more than a year. Patients might otherwise have been a good candidate for systemic treatment, so you might have been able to spare them the toxicity.
In the case of cabozantinib, the PFS in the study arm was roughly 11 months compared with approximately 4 months in the placebo arm. That sounds a little bit worse, but again, this was a different patient population with a more aggressive type of thyroid cancer. The type of RET
mutation you detect does not influence the drug you’re using or tell you when to start treatment, [which] is really based on whether they have disease progression. Ultimately what counts is not calcitonin or CA levels, but radiographic progression.
Do all MTCs turn more aggressive?
At this point, we don’t really know what prompts cancers to enter the accelerated phase. The vast majority of patients eventually enter that phase and it’s impossible to predict when that’s going to happen. There must be some additional genetic event that occurs. When that occurs is probably largely due to chance. It’s probably also not just one process but perhaps a number of events that trigger those tumors to become more aggressive.