SAN DIEGO — Sunitinib appears to exhibit significant antitumor activity in patients with advanced differentiated thyroid cancer. In addition, it is relatively well tolerated, suggesting that it may have clinical benefit, according to a phase 2 clinical trial.
Results from the single-center, open-label, nonrandomized trial, which were presented at ENDO 20151, showed that sunitinib — a multikinase inhibitor that targets the vascular endothelial growth factor receptor (VEGFR) — could potentially be used as an effective adjunctive treatment in patients with advanced differentiated thyroid cancer.
Principal Investigator Kenneth Burman, MD, who is chief of the endocrine section at MedStar Washington Hospital Center in Washington, D.C., said that while sunitinib is not a cure, it appears that it may slow the progression of disease.
In the study, Dr. Burman and his colleagues tested the treatment effect of sunitinib in 23 patients with advanced-stage differentiated thyroid cancer who had undergone at least one course of radioactive iodine treatment.
In this cohort, 16 patients (70%) had papillary thyroid cancer and seven patients (30%) had follicular and poorly differentiated thyroid cancer. Lung metastasis was documented in 21 patients (91%) and bone metastasis was documented in eight patients (35%).
The researchers measured progression-free survival (PFS) as well as the response of tumor growth to sunitinib using the Response Evaluation Criteria in Solid Tumors (RECIST). Patients received a starting daily dose (37.5 mg) of oral sunitinib.
The researchers found that the overall median PFS was 241 days (95% CI, 114-506). When compared with historical controls from the literature, the survival curve was more favorable, demonstrating a statistically significant difference (P=.02).
Overall, 26% of the patients (n=6) achieved a partial response, and 57% of the patients (n=13) had stable disease for a clinical benefit rate of 83%. Mean best response was a 16.9% decrease in tumor sum from baseline.
The most common adverse events included decreases in blood cell counts, especially leukocytes, diarrhea, fatigue, hand–foot skin reaction, nausea, musculoskeletal pain and hypertension.
“The median PFS was 241 days with interquartile limits of 114 to 518,” said study co-investigator Athanasios Bikas, MD, who is with MedStar Health Research Institute. “There were side effects as with all [tyrosine kinase inhibitors], because these drugs target a wide variety of tyrosine kinases all over human body, but the vast majority were grade 1 and 2 (mild and moderate). There were noted some rare grade 3 events, but no grade 4 or grade 5.”
The findings from this study suggest that the PFS using sunitinib was comparable to that previously reported for sorafenib, according to the researchers.
“There are two other phase 2 clinical trials of sunitinib in thyroid cancer2,3,” Dr. Bikas told Endocrinology Advisor. “The take-home point is that sunitinib has a potential role in advanced differentiated thyroid cancer, but this has to be examined and confirmed in a larger phase 3 clinical trial. Also, it is important due to recent reports demonstrating that patients who fail a TKI after a period of time, but respond to the treatment with a different TKI.”
Sunitinib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced renal cell carcinoma (RCC), imatinib-refractory gastrointestinal stromal tumors (GIST) after disease progression and progressive pancreatic neuroendocrine tumors.
Further trials are now planned in patients with advanced differentiated thyroid cancer.
- Bikas A et al. Abstract OR44-5. Presented at: The Endocrine Society’s 97th Annual Meeting & Expo (ENDO 2015); March 5-8, 2015; San Diego.
- Cohen et al. J Clin Oncol. 2008;26S:6025.
- Carr et al. Clin Cancer Res. 2010;16(21):5260-5268.