According to research published in the Journal of Clinical Oncology.1
The researchers noted that approximately 70% of patients with DTC carried mutations that activated the RAS-ERK pathway, which suppresses gene expression necessary for iodine uptake and compromises the effectiveness of RAI.
Researchers conducted the Phase 3 ASTRA trial (ClinicalTrials.gov Identify: NCT01843062) to determine whether selumetinib, an MEK 1/2 inhibitor, can improve the efficacy of RAI in the adjuvant setting in patients with DTP who are at high risk of primary treatment failure.
The study included 233 patients who were randomized to receive selumetinib 75 mg orally twice daily (155 patients) or placebo (78 patients) for approximately 5 weeks.
On treatment days 29 through 31, all patients received RAI (131I; 100 mCi/3.7 GBq) boosted with recombinant human thyroid-stimulating hormone (0.9 mg), followed by 5 days of selumetinib or of a placebo.
The primary endpoint was 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).
Similarly, there was no significant difference in CR rates at 18 months between the selumetinib and placebo arms for patients with:
- BRAF Where 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).
Additionally, there were no significant differences by histology, age, gender, 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. Acneiform dermatitis (7%) was the most common AE with selumetinib. There were no treatment-related deaths.
“Postoperative disease risk stratification identified patients with DTP at high risk of primary treatment failure, although adding selumetinib to adjuvant RAI failed to improve the CR rate for these patients,” they wrote. concluded the researchers. “Future strategies should focus on selecting drugs appropriate to the tumor genotype and maintaining drug dosing to optimize RAI efficacy.”
Disclosures: This research was partially funded by AstraZeneca. Some study authors have declared affiliations with biotechnology, 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 Radioiodine 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