KEY TAKEAWAYS
- Phase II ASTRA trial named assessed whether combining Selumetinib with adjuvant RAI enhances complete remission rates in high-risk DTC patients.
- A randomized, double-blind, placebo-controlled trial design was used to allocate patients with high-risk DTC tumors exceeding 4 cm and gross extrathyroidal extension beyond the T4 disease.
- N1a/N1b disease with at least one metastatic lymph node measuring at least 1 cm or at least five lymph nodes of any size, to receive either 75mg.
- The primary endpoint was the complete response rate 18 months after radioactive iodine therapy.
- Selumetinib and adjuvant RAI did not improve complete response rates in high-risk DTC patients.
The administration of Selumetinib could enhance the radioactive iodine (RAI) avidity in unresponsive tumors to RAI treatment. The study assessed the efficacy of combining selumetinib with adjuvant RAI in enhancing complete remission (CR) rates among patients diagnosed with differentiated thyroid cancer (DTC) at a high risk of primary treatment failure, compared to the use of RAI alone. The ASTRA study, identified on ClinicalTrials.gov as NCT01843062, is a phase III clinical trial conducted internationally. It is designed as a randomized, double-blind, placebo-controlled trial. Individuals diagnosed with differentiated thyroid cancer (DTC) who are at a heightened risk of primary treatment failure, characterized by a primary tumor exceeding 4 cm, gross extrathyroidal extension beyond the thyroid gland (T4 disease), or N1a/N1b disease with at least one metastatic lymph node measuring at least 1 cm or at least five lymph nodes of any size, were subjected to a randomized 2:1 allocation to receive either 75 mg of selumetinib orally twice daily or placebo for roughly five weeks, without any form of stratification. During the treatment period from day 29 to day 31, the patient received recombinant human thyroid-stimulating hormone (0.9 mg) to stimulate the uptake of RAI (131I; 100 mCi/3.7 GBq). A 5-day course of selumetinib or placebo followed this. The primary endpoint, the complete response rate 18 months after radioactive iodine therapy, was evaluated in the intention-to-treat cohort.
400 individuals were registered between August 27, 2013, and March 23, 2016, with 233 randomly allocated (67% selumetinib, n = 155; 33% placebo, n = 78). There was no notable disparity in the CR rate 18 months following the RAI administration. The selumetinib group comprised 62 individuals (40%), while the placebo group had 30 individuals (38%). The odds ratio was 1.07 (95% CI, 0.61 to 1.87), and the P-value was .8205. A total of 25 out of 154 patients (16%) who received selumetinib reported treatment-related adverse events of grade ≥ 3, whereas none of the patients who received a placebo reported such events. The prevailing untoward incident observed with selumetinib was dermatitis acneiform, affecting 11 individuals (7%). There were no fatalities reported as a result of treatment. Identifying postoperative pathologic risk stratification in patients with differentiated thyroid cancer (DTC) can determine those at high risk of primary treatment failure. However, administering selumetinib with adjuvant radioactive iodine (RAI) did not improve these patients’ complete response (CR) rate. Prospective tactics should prioritize drug selection tailored to the genotype of the tumor and the maintenance of appropriate drug dosing to enhance the effectiveness of RAI.
Source: https://pubmed.ncbi.nlm.nih.gov/35192411/
Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT01843062
Ho AL, Dedecjus M, Wirth LJ, Tuttle RM, Inabnet WB 3rd, Tennvall J, Vaisman F, Bastholt L, Gianoukakis AG, Rodien P, Paschke R, Elisei R, Viola D, So K, Carroll D, Hovey T, Thakre B, Fagin JA; 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. 2022 Jun 10;40(17):1870-1878. doi: 10.1200/JCO.21.00714. Epub 2022 Feb 22. PMID: 35192411; PMCID: PMC9851689.
