Phase II trial of sunitinib in medullary thyroid cancer (MTC).

5504 Background: There is no standard treatment for MTC not amenable to surgery or radiotherapy. Sunitinib is an oral multikinase inhibitor against RET, VEGFR2, PDGFR, and c-KIT. We conducted an open-label multicenter phase II trial to determine the efficacy of sunitinib in patients (pts) with MTC and whether RET mutations can predict response. Methods: Pts with MTC who had evidence of disease progression within the prior 6 months and were not amenable to surgery or radiotherapy were treated with sunitinib 50 mg at a 4/2 week schedule. Responses were monitored by RECIST and serum calcitonin measurements every 12 weeks. Results: 25 pts were enrolled from 11/2006 to 08/2009; one pt was deemed ineligible and never received drug. Median follow-up was 11 months (range, 1-34); median age was 51 years (23-74); 12 pts (50%) were male. 23 pts were evaluable for response. To date, RET activating mutations were found in 11 (85%) of 13 analyzed tumors (8 somatic and 3 germline). Partial response (PR) was achieved in 8 (35%) pts with a median duration of response of 37 weeks (22-106+). 13 (57%) had stable disease (SD) with a median duration of 32 weeks (12-147+). Among those who progressed, the median time-to-progression was 28 weeks. 13 pts remain on study. The most common treatment-related adverse events were fatigue, lymphopenia, neutropenia, nausea, diarrhea, mucositis and palmar-plantar erythema (PPE). Two pts died during the trial due to non-related toxicities. There was one case of grade 4 neutropenia. Grade 3 events were: lymphopenia, 6 pts (25%); neutropenia, 5 pts (21%); PPE, 4 pts (17%); and mucositis, 3 pts (13%). One pt discontinued on day 15 due to grade 3 fatigue. 10 pts showed a decrease in calcitonin levels greater than 30%. Further genotyping for RET mutations is in progress and to date, in the pts with an activating RET mutation, the 1-year probability of progression free survival was 88% (95% CI, 43-98%). Evidence of PR or SD greater than 24 weeks was observed in 7 of 9 MTC pts with a M918T RET mutation. Conclusions: Sunitinib has activity in MTC, with an overall response rate of 35% and clinical benefit rate (PR + SD) of 91%. Evidence of clinical benefit has been observed in pts with and without RET mutations and the M918T RET mutation may be associated with a durable response. No significant financial relationships to disclose.