|The following article features coverage from the American Thyroid Association (ATA) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
The addition of the MEK1/2 inhibitor selumetinib to adjuvant radioactive iodine (RAI) did not improve outcomes among patients with high-risk nonmetastatic differentiated thyroid cancer (DTC), according to results from a phase 3 trial presented at the 88th Annual Meeting of the American Thyroid Association in Washington, D.C.1
The RAF/MEK/ERK pathway influences the efficacy of RAI against DTC by downregulating thyroid-specific gene expression. The purpose of the phase 3 ASTRA study was to determine if the addition of a MEK1/2 inhibitor would improve the complete remission rate (CRR) after RAI for patients with DTC at high-risk of primary treatment failure.
The ASTRA trial randomly assigned 233 adult patients with nonmetastatic DTC at high-risk of treatment failure after thyroidectomy 2:1 to receive 75 mg of selumetinib twice daily or placebo. Patients were treated approximately 4 weeks prior to and for 5 days after RAI. The primary end point was CRR at 18 months without further therapy after RAI. Secondary end points included 18-month CRR stratified by BRAF/NRAS mutation status, safety, and tolerability.
There was no significant difference in CRR among the 157 evaluable patients. The CRR was 40% in the selumetinib arm compared with 38.5% in the placebo arm (odds ratio [OR], 1.07; 95% CI, 0.61-1.87; P = .82).
The CRR was similar among patients with or without BRAF/NRAS mutations. Among patients with mutations, the CRR was 37.4% and 41.2% in the selumetinib and placebo arms, respectively (OR, 0.85; 95% CI, 0.42-1.73; P = .65). The CRR for patients without the mutations was 44.4% and 31.3% among the selumetinib and placebo groups, respectively (OR, 1.76; 95% CI, 0.54-6.35; P = .35).
Adverse events (AEs) were reported by 98% and 75% of patients treated with selumetinib or placebo, respectively. Selumetinib resulted in more reports of grade 3 or higher events (18%) compared with placebo (1%), and 18 patients discontinued selumetinib due to AEs.
The authors concluded that “adding selumetinib to postoperative RAI did not improve CRR in this high-risk population.” They noted, however, that the safety profile of selumetinib was consistent with previous reports. “Assessing efficacy of other MAPK inhibitors may be warranted in patients with BRAF/NRAS mutations,” the authors wrote.
Read more of Cancer Therapy Advisor‘s coverage of the ATA 2018 meeting by visiting the conference page.
- Ho A, Dedecjus M, Wirth LJ, et al. ASTRA: a phase III, randomized, placebo-controlled study evaluating complete remission rate (CRR) with short-course selumetinib plus adjuvant radioactive iodine (RAI) in patients (pts) with differentiated thyroid cancer (DTC). Presented at: the 88th Annual Meeting of the American Thyroid Association; Washington, D.C.: October 3-7, 2018. Abstract short call oral 8.