MEK1/2 Inhibitor After RAI Fails to Improve Outcomes in High-Risk Nonmetastatic Thyroid Cancer

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The addition of selumetinib to radioactive iodine did not improve the complete remission rate among patients with high-risk nonmetastatic differentiated thyroid cancer.
The addition of selumetinib to radioactive iodine did not improve the complete remission rate among patients with high-risk nonmetastatic differentiated thyroid cancer.
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.

Reference

  1. 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.

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