PURPOSE: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly
selective inhibitor of
vascular endothelial growth factor receptors 1, 2, and 3;
platelet-derived growth factor receptor; and Kit in advanced
medullary thyroid cancer (MTC). PATIENTS AND METHODS: Patients with locally advanced or
metastatic, progressive or
symptomatic MTC received motesanib 125 mg/d orally for up to 48 weeks or until unacceptable
toxicity or disease progression. The primary end point was objective response by independent review. Other end points included duration of response, progression-free survival, safety,
pharmacokinetics, and changes in
tumor markers. RESULTS: Of 91 enrolled patients who received motesanib, two (2%) achieved objective response (95% CI, 0.3% to 7.7%); their duration of response was 32 weeks (censored) and 21 weeks (disease progressed). Eighty-one percent of patients had stable disease (48% had durable stable disease > or = 24 weeks), 8% had disease progression as best response, and 9% were not evaluated; 76% experienced a decrease from baseline in target
lesion measurement.
Median progression-free survival was 48 weeks (95% CI, 43 to 56 weeks). Among patients with
tumor marker analysis, 69 (83%) of 83 and 63 (75%) of 84 had decreased serum
calcitonin and
carcinoembryonic antigen during treatment, respectively, compared with baseline. The most common treatment-related
adverse events were
diarrhea (41%), fatigue (41%),
hypothyroidism (29%),
hypertension (27%), and anorexia (27%). In
pharmacokinetic analyses, motesanib trough concentrations were lower compared with differentiated
thyroid cancer patients from the same study. CONCLUSION: Although the objective
response rate was low, a significant proportion of MTC patients (81%) achieved stable disease while receiving motesanib.
