1329PEfficacy and safety of vandetanib for patients with advanced and progressive medullary thyroid cancer (MTC) as systemic treatment beyond first-line therapy

Background: Vandetanib has demonstrated efficacy in advanced MTC in a large phase III trial (ZETA trial, JCO 2012). However, the study had several limitations that impact in the daily clinical practice, such as the efficacy in patients (pts) with documented disease progression or beyond first-line therapy who have a worse prognosis. Methods: Pts with advanced unresectable MTC with previous radiologically documented disease progression were included in the Spanish National Database of the Rare Cancer Working Group (GETHI). Pts started treatment with vandetanib 300mg qd as initial dose, with dose reductions allowed as per toxicity. Baseline characteristics, progression free survival (PFS), response rate (RR), correlation with biomarkers and toxicity data were reviewed retrospectively in first, second and third line setting. The program was validated by regulatory authorities and all patients signed and informed consent form. Results: 59 pts (med age:48y; male 61%) were included. 14% had RET mutations. Vandetanib was given as first line in 61%, second-line in 22% and third-line therapy in 17% of pts. RR and median PFS in first, second and third-lines were 47%, 53% and 40% (p 0.85%) and 16.8, 13.6 and 11.5 months (p 0.94) respectively. No correlation was found between calcitonin or CEA reduction and RR. However, CEA level decrease (30% versus baseline) appeared to predict PFS longer than 11 months (p 0.028). Treatment was well tolerated and dose reduction was needed in 23% to handle toxicity. Main side effects were grade 1-2 including fatigue (22%), skin rash (19%), hypertension (14%) and diarrhea (14%). Most frequent grade 3 toxicity was oral mucositis (3%). Conclusions: Probability of tumor shrinkage with vandetanib is maintained throughout treatment lines despite of a trend of reduced benefit in PFS beyond first-line in a cohort of pts with a worse prognosis. CEA reduction may predict longer PFS. Safety is maintained regardless prognosis and prior therapies. Legal entity responsible for the study: Spanish Rare Cancer Working Group (GETHI). Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.