Outcomes of children with hereditary medullary thyroid carcinoma (MTC) treated with vandetanib.

Abstract

10540 Background: Vandetanib is well tolerated and active in children with advanced or metastatic hereditary MTC (NCT00514046) [data cutoff 7/2011; Clin Cancer Res. 2013 Aug 1;19(15):4239-48]. We report outcomes as of 1/2017. Methods: We monitored toxicities, RECISTv1.0, carcinoembryonic antigen (CEA), and calcitonin (CT) response. Patients (pts) removed from the vandetanib trial were followed on a natural history study (NCT01660984). Results: Of 17 pts (8 male, age 13 years (9-17)*) enrolled, 1 was lost to follow-up. Of the 16 pts analyzed, 15 had a RET p.M918T germline mutation. The duration of vandetanib therapy was 5.6 years (0.1-9.2+) with treatment ongoing in 8 pts. Best response was partial response (PR) in 10, stable disease (SD) in 5, and progressive disease (PD) in 1 pt. Time to achieve PR (n = 10) was 0.6 years (0.4-2.4). Time to best response (n = 16) was 1.5 years (0.1-4.1). Duration of response was 5.1 years (1.3-8.6+) in pts with PR and 4.8 years (0.6-7.3+) in pts with SD. Seven of 8 pts with PD subsequently received sunitinib, sorafenib, and/or cabozantinib. Disease progression occurred as increase in target (n = 2), non-target/new lesions (n = 5), or CT/CEA (n = 1). Six pts died from disease 2.1 years (0.4-4.3) after stopping vandetanib. Progression free survival was 6.2 years (95% CI 3.0-na) and overall survival was 7.9 years (95% CI 5.9-na).Pts had no difference in enrollment age, baseline CT/CEA, or tumor size per response categories (n = 16). Rate of CEA/CT decrease during initial 4 months of treatment was not associated with PR/SD compared to PD (n = 16). While on vandetanib, 6 pts with PD had CEA or CT doubling time (DT) of < 2 years within 1 year prior to PD. All pts with ongoing PR/SD had CEA and CT DT > 2 years while on vandetanib. No pts came off treatment for toxicity. Dose reductions occurred in 8 pts for grade (gr) 2 weight loss (n = 2), palpitations (n = 1), arrhythmia (n = 1), elevated creatinine (n = 1), diarrhea (n = 2), and gr 3 constipation (n = 1). Conclusions: Many children with hereditary MTC sustained PR/SD on vandetanib. However, half ultimately developed PD and died from disease despite treatment with other targeted therapies. CEA/CT DT < 2 years within 1 year of progression on vandetanib may be associated with PD. *Median (range)