Recombinant human thyrotropin preferred option for RAI in predominantly intermediate-risk differentiated thyroid cancer: JAMA

Differentiated thyroid cancers constitute a major portion of thyroid cancers. Surgery, postoperative radioactive iodine (¹³¹I or RAI) therapy, and personalized thyroid hormone therapy are some of the treatment modalities for thyroid cancers. Previous guidelines recommended routine RAI therapy for patients with intermediate- or high-risk DTC and recombinant human thyrotropin instead of undergoing thyroid hormone withdrawal (THW) for low- or intermediate-risk- DTC. RAI dose is another important issue in the management of DTC as greater therapeutic efficacy but also a higher incidence of adverse effects. As there is ambiguity on the appropriate dose of RAI for patients with intermediate-risk DTC, researchers from China conducted a trial to compare the efficacy and safety of recombinant human thyrotropin (SNA001) with thyroid hormone withdrawal (THW) plus 3.7 GBq RAI in patients with intermediate-risk DTC.

An open-label, non-inferior, phase 3 randomized clinical trial was conducted at 19 sites in China from April 16, 2020, to September 9, 2021, with a follow-up period of 8 months. Patients aged 18 to 70 years with DTC who had undergone a total or near-total thyroidectomy and had no distant metastasis were enrolled in the trial. Individuals were randomly assigned 1:1 to receive SNA001, 0.9 mg, intramuscular injection daily for 2 days or to undergo thyroid hormone withdrawal for 3 to 6 weeks. The primary end point of measurement was the success rate after 6 to 8 months of RAI therapy. Success was defined as a negative diagnostic whole-body scan result and a stimulated thyroglobulin level of less than 1.0 ng/mL. Statistical analysis followed the full analysis and per-protocol analysis sets and was performed between November 18, 2021, and April 18, 2022.

Findings:

• A total of 307 patients were randomized 154 to the SNA001 group and 153 to the THW group.
• About 192 females [62.5%] with a median [range] age of 40 [19-69] years participated in the trial.
• Baseline characteristics were evenly matched between the 2 groups.
• RAI therapy was successfully found to be non-inferior between groups, with success rates of 43.8% in the SNA001 group and 47.1% in the THW group
• Forty-six patients (29.9%) in the SNA001 group reported adverse events compared with 90 (58.8%) in the THW group during RAI therapy (P < .001).
• No treatment-related adverse events leading to discontinuation and drug modification occurred in the SNA001 group.

Thus, the study found that SNA001 was found to be non-inferior to THW plus 3.7 GBq RAI in patients with predominantly intermediate-risk DTC. The researchers also found that it demonstrated a favorable safety profile compared with THW and had a lower incidence of adverse events. Overall, this trial was a viable and safe alternative to thyroid hormone withdrawal for RAI therapy preparation in patients with intermediate-risk differentiated thyroid cancer.

Further reading: Tan H, Gu Y, Xiu Y, et al. Recombinant Human Thyrotropin Plus Radioactive Iodine Among Patients With Thyroid Cancer: A Noninferiority Randomized Clinical Trial . JAMA Netw Open. 2024;7(11):e2443407. doi:10.1001/jamanetworkopen.2024.43407.