Redifferentiation therapy resensitizes some radioactive iodine-refractory thyroid cancer

CHICAGO — Redifferentiation therapy with MEK inhibitor and/or BRAF inhibitor therapy resensitized some patients with metastatic radioactive iodine-refractory thyroid cancer to radioactive iodine, according to retrospective study results presented at the Annual Meeting of the American Thyroid Association.

“We now need prospective studies with control arms to further validate these findings and to evaluate the benefit in survival,” Rosa Falcone, MD, researcher in the department of translational and precision medicine at Sapienza University of Rome, said during a presentation.

Radioactive iodine (RAI)-refractory thyroid cancers lose their ability to concentrate iodide efficiently, making RAI therapy ineffective.

Prior studies showed improved RAI uptake among patients with BRAF-mutant disease who received BRAF inhibitors, as well as among those without BRAF mutations who received MEK inhibitor treatment, according to study background.

Falcone and colleagues evaluated 41 patients (median age, 56 years; range, 34-74; 59% women) with metastatic RAI-refractory papillary, follicular or poorly differentiated thyroid cancer who underwent redifferentiation therapy using kinase inhibitors with single-agent or combination BRAF inhibitor/MEK inhibitor treatment.

Eligible patients needed to be followed for at least 6 months after redifferentiation RAI therapy.

The researchers evaluated clinical response to redifferentiation therapy after RAI and after kinase inhibitor discontinuation. Investigators assessed PFS, time to progression, time off kinase inhibitor therapy and response by RECIST 1.1 criteria.

Thirty-one patients (76%) had BRAF V600E mutations and nine (22%) had RAS mutations.

Investigators deemed 19 patients unevaluable for response to RAI therapy because they either did not receive it or continued kinase inhibitor therapy after receiving it.

The analysis included 22 patients who received I-131 at a median dose of 188 mCi, after which kinase inhibitor therapy was discontinued. In the majority (79%) of cases, kinase inhibitor therapy had been initiated due to progressive disease.

The majority of patients showed uptake on diagnostic whole body scan (78%), and on both diagnostic and post-RAI scans (93%).

Median follow-up was 18.5 months after RAI. At that time, 15 patients (40%) had stable disease as best response after RAI, two patients (9%) had achieved partial response and five (23%) had experienced disease progression.

Median time to progression after RAI administration was 20 months, and median PFS from the start of kinase inhibitor therapy was 29 months. Researchers reported no statistically significant differences in these results based on BRAF mutation status.

Median time off systemic treatment was 24 months.

Researchers performed thyroglobulin analysis on evaluable patients who had no thyroglobulin antibodies. Results showed thyroglobulin increased after kinase inhibitor therapy (mean, 1,254 ng/mL vs. 646 ng/mL), decreased at 6 months (mean, 499 ng/mL) and began to increase again at the time of progression (mean, 817 ng/mL).

“A possible advantage of the median time to progression of 20 months after redifferentiation strategy is to reduce the exposure to kinase inhibitors, which may limit toxicities and the costs of treatment,” Falcone said. – by Jennifer Southall

Reference:

Falcone R, et al. Short Call Oral Abstract 10. Presented at: Annual Meeting of the American Thyroid Association; Oct. 30-Nov. 3, 2019; Chicago.

Disclosures: Falcone reports no relevant financial disclosures.