ASTRA
Adding a MEK inhibitor to boost iodine uptake before ablation did not improve complete remission rates, cooling the 'redifferentiation for everyone' idea.
Overview
ASTRA, trial NCT01843062 sponsored by AstraZeneca and reported in 2019, found that adding the MEK inhibitor selumetinib to boost iodine uptake before adjuvant radioiodine in high-risk differentiated thyroid cancer did not improve complete remission rates, cooling the idea of redifferentiation for everyone. It enrolled 400 patients and randomised 233 of them 2:1 to selumetinib or placebo with radioiodine (Ho and colleagues, Journal of Clinical Oncology 2022) and found no difference in complete remission at eighteen months. Nuclide links it to thyroid cancer, radioiodine therapy, kinase inhibitors, the MAPK pathway and the pairing of MAPK inhibitor redifferentiation followed by radioiodine. Redifferentiation remains reserved for selected radioiodine-refractory patients, where small series show MEK or BRAF and MEK inhibitors restore uptake in about half, and whether that selected use can be proved in a randomised trial is the open question.
- 40 vs 38.5 out of 100 had no sign of cancer on scans or tests with Selumetinib + RAI compared with Placebo + RAI; 1.5 more per 100.
- Roughly one extra person helped for every 67 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: High-risk differentiated thyroid cancer: selumetinib + adjuvant radioiodine vs placebo + radioiodine. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
233 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Complete remission at 18 monthsprimary | Selumetinib + RAI | - | 40% | - | - | link |
| Placebo + RAI | - | 38.5% |
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