CHICAGO — Apatinib demonstrated encouraging clinical activity among Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer, according to results of a small phase 2 study presented at the Annual Meeting of the American Thyroid Association.
“We know that up to 20% of patients with differentiated thyroid cancer develop distant metastases and two-thirds will eventually become refractory to radioactive iodine treatment. With a 10-year survival rate of less than 10%, there is a significant clinical issue here,” Yan-Song Lin, MD, researcher in the department of nuclear medicine at Peking Union Medical College Hospital in China, said during a presentation.
Few treatment options are available for progressive radioactive iodine-refractory differentiated thyroid cancer, contributing to an unfavorable prognosis for this patient population.
Apatinib (YN968D1, Elevar Therapeutics) — a novel, oral small molecule tyrosine kinase inhibitor that selectively inhibits VEGFR2 — induced rapid responses among patients who received treatment in either two or six 28-day cycles. The agent also appeared safe in short-term evaluations.
However, long-term data are limited.
Lin and colleagues evaluated apatinib in two doses for 20 Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer.
Researchers started 10 patients on apatinib dosed at 500 mg daily. The other 10 patients started with a dose of 750 mg daily.
Treatment continued until disease progression, unmanageable toxicity, study withdrawal or death. However, study protocol allowed for treatment interruption and successive dose decrease (250 mg/level) due to adverse events.
Median follow-up was 13.8 months (interquartile range, 7.4-32.3).
Lin and colleagues reported an overall response rate of 80%, including ORRs of 90% among patients started on the 750 mg dose and 70% for those started on the 500 mg dose. The over disease control rate was 100% with the 750 mg dose and 90% with the 500 mg dose.
Median PFS was 18.4 months (95% CI, 0-37.4) for the entire cohort, 34.9 months (95% CI, 0-74.3) with the 750 mg schedule and 12.9 months (95% CI, 9.6-16.2) with the 500 mg schedule.
All patients experienced adverse events, the majority of which were grade 1 or grade 2.
The most common adverse events included hand-foot skin reaction (85%), proteinuria (75%), diarrhea (60%) and hypertension (55%).
“There were several limitations to our study, including the relatively small sample size and study enrollment was sequential rather than blinded,” Lin said. “We currently have a randomized, double-blind, phase 3 study underway in progressive radioactive iodine-refractory differentiated thyroid cancer with 75% of total enrollment complete.” – by Jennifer Southall
Zhang X, et al. Short Call Oral Abstract 8. Presented at: Annual Meeting of the American Thyroid Association; Oct. 30-Nov. 3, 2019; Chicago.
Disclosures: Lin reports receiving financial support from Jiangsu Hengrui Medicine Co. LTD, China.