Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation

Abstract

Purpose: We conducted a phase II study to assess the efficacy of continuous dosing of sunitinib in patients with flurodeoxyglucose positron emission tomography (FDG-PET)-avid, iodine-refractory well-differentiated thyroid carcinoma (WDTC) and medullary thyroid cancer (MTC) and to assess for early response per FDG-PET.

Experimental design: Patients had metastatic, iodine-refractory WDTC or MTC with FDG-PET-avid disease. Sunitinib was administered at 37.5 mg daily on a continuous basis. The primary end point was response rate per Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included toxicity, overall survival, and time to progression. We conducted an exploratory analysis of FDG-PET response after 7 days of treatment.

Results: Thirty-five patients were enrolled (7 MTC, 28 WDTC), and 33 patients were evaluable for disease response. The primary end point, objective response rate per RECIST, was 11 patients (31%; 95% confidence interval, 16-47%). There were 1 complete response (3%), 10 partial responses (28%), and 16 patients (46%) with stable disease. Progressive disease was seen in 6 patients (17%). The median time to progression was 12.8 months (95% confidence interval, 8.9 months-not reached). Repeat FDG-PET was done on 22 patients. The median percent change in average standardized uptake values was -11.7%, -13.9%, and 8.6% for patients with RECIST response, stable disease, and progressive disease, respectively. Differences between response categories were statistically significant (P = 0.03). The most common toxicities seen included fatigue (11%), neutropenia (34%), hand/foot syndrome (17%), diarrhea (17%), and leukopenia (31%). One patient on anticoagulation died of gastrointestinal bleeding.

Conclusion: Continuous administration of sunitinib was effective in patients with iodine-refractory WDTC and MTC. Further study is warranted.

©2010 AACR.

Figures

Figure 1

(A) Maximum percentage change in target lesions from baseline in all patients with evaluable disease (n=33). (1 patient removed from study due to adverse event prior to evaluation, 1 patient did not have measurable disease per RECIST criteria at baseline). Blue bars: well-differentiated thyroid cancer; Green bars: medullary thyroid cancer. (B) Kaplan-Meier estimate of time to progression. The median time to progression per Kaplan-Meier analysis is 12.8 months (95%CI, 8.9 months – not reached). (C) Kaplan-Meier estimate of overall survival. The median overall survival has not been reached, 9 patients have died during the follow up period.

Figure 1

(A) Maximum percentage change in target lesions from baseline in all patients with evaluable disease (n=33). (1 patient removed from study due to adverse event prior to evaluation, 1 patient did not have measurable disease per RECIST criteria at baseline). Blue bars: well-differentiated thyroid cancer; Green bars: medullary thyroid cancer. (B) Kaplan-Meier estimate of time to progression. The median time to progression per Kaplan-Meier analysis is 12.8 months (95%CI, 8.9 months – not reached). (C) Kaplan-Meier estimate of overall survival. The median overall survival has not been reached, 9 patients have died during the follow up period.

Figure 1

(A) Maximum percentage change in target lesions from baseline in all patients with evaluable disease (n=33). (1 patient removed from study due to adverse event prior to evaluation, 1 patient did not have measurable disease per RECIST criteria at baseline). Blue bars: well-differentiated thyroid cancer; Green bars: medullary thyroid cancer. (B) Kaplan-Meier estimate of time to progression. The median time to progression per Kaplan-Meier analysis is 12.8 months (95%CI, 8.9 months – not reached). (C) Kaplan-Meier estimate of overall survival. The median overall survival has not been reached, 9 patients have died during the follow up period.

Figure 2

Average SUV percent change by type of RECIST response Percent changes in average SUVs from baseline to one week of sunitinib by RECIST response criteria, categorized as responsive (n=6), stable (n=12), or progressive disease (n=4). The P-value was obtained from a global F-test.