Adding selumetinib to postoperative radioactive iodine (RAI) does not improve the 18-month complete remission (CR) rate in patients with high-risk differentiated thyroid cancer (DTC), according to research published in the Journal of Clinical Oncology.1

The researchers noted that roughly 70% of patients with DTC harbor mutations that activate the RAS-ERK pathway, which suppresses the gene expression required for iodine uptake and compromises RAI efficacy.

The researchers conducted the phase 3 ASTRA trial ( Identifier: NCT01843062) to investigate whether selumetinib, a MEK 1/2 inhibitor, can enhance RAI efficacy in the adjuvant setting in patients with DTC who are at high risk of primary treatment failure.

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The study included 233 patients who were randomly assigned to receive selumetinib at 75 mg orally twice daily (155 patients) or placebo (78 patients) for approximately 5 weeks.

On treatment days 29 to 31, all patients received recombinant human thyroid-stimulating hormone (0.9 mg)-stimulated RAI (131I; 100 mCi/3.7 GBq), followed by either 5 days of selumetinib or placebo.

The primary endpoint was the CR rate at 18 months, and there was no significant difference between the selumetinib and placebo arms — 40% and 38%, respectively (odds ratio [OR], 1.07; 95% CI, 0.61-1.87; P =.8205).

Likewise, there was no significant difference in CR rates at 18 months between the selumetinib and placebo arms for patients with:

  • BRAF or NRAS mutations — 37% and 41%, respectively (OR, 0.85; 95% CI, 0.42-1.73; P =.6549)
  • Mutant BRAF only — 36% and 37%, respectively (OR, 0.96; 95% CI, 0.45-2.12; P =.9242)
  • Wild-type BRAF — 44% and 38%, respectively (OR, 1.28; 95% CI, 0.50-3.40; P =.6112).

In addition, there were no significant differences by histology, age, sex, or ethnicity.

Grade 3 or higher treatment-related adverse events (AEs) occurred in 16% of patients in the selumetinib arm and 0% in the placebo arm.  Dermatitis acneiform (7%) was the most common AE with selumetinib. There were no treatment-related fatalities.

“Postoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients,” the researchers concluded. “Future strategies should focus on tumor genotype-tailored drug selection and maintaining drug dosing to optimize RAI efficacy.”

Disclosures: This research was partially supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Ho AL, Dedecjus M, Wirth LJ, et al; ASTRA investigator group. Selumetinib plus adjuvant radioactive iodine in patients with high-risk differentiated thyroid cancer: a phase III, randomized, placebo-controlled trial (ASTRA). J Clin Oncol. Published online February 22, 2022. doi:10.1200/JCO.21.00714