Phase 3 trial of Selpercatinib in advanced RET-mutated medullary thyroid cancer

Selpercatinib/Selpercatinib is a highly selective and potent RET inhibitor that was effective against advanced RET-mutant medullary thyroid cancer in phase 1-2 trials, but its efficacy compared with approved multikinase inhibitors is unclear.

A phase 3 randomized trial was conducted comparing seputinib as first-line treatment with physician's choice of cabozantinib or vandetanib (control group). Eligible patients had documented disease progression within 14 months prior to enrollment. The primary endpoint of the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. After disease progression, patients in the control group were allowed to cross over to seputinib. Treatment failure-progression-free survival assessed by blinded independent central review was a secondary alpha control endpoint and was tested only if progression-free survival was significant. Other secondary endpoints include overall response and safety.

A total of291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival, as assessed by blinded independent central review, was not reached in the seputinib group and was 16.8 months (95% CI, 12.2-25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16-0.48; P<0.001). The 12-month progression-free survival rate was 86.8% (95% CI, 79.8-91.6) in the seputinib group and 65.7% (95% CI, 51.9-76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the seplutenib arm compared with 13.9 months in the control arm (hazard ratio for disease progression, discontinuation of treatment-related adverse events, or death, 0.25; 95% CI, 0.15-0.42; P<0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1-91.0) in the seputinib group and 62.1% (95% CI, 48.9-72.8) in the control group. The overall response rate was 69.4% (95%CI, 62.4-75.8) in the cepotinib group and 38.8% (95%CI, 29.1-49.2) in the control group.

Adverse events led to dose reductions in 38.9% of patients in the seprotinib group and 77.3% in the control group, with 4.7% and 26.8% of patients discontinuing treatment, respectively. Compared with cabozantinib or vandetanib, cepretinib demonstrated improved progression-free survival and treatment failure-free survival in patients with RET-mutated medullary thyroid cancer.

Up to now, the original drug is sold in China under the name of seputinib, but it is not included in medical insurance. SpecificationsThe price of each box of 80mg*56 capsules may be more than 10,000 yuan. There are European and American versions of the original drugs sold overseas, with the price of each box ranging from 20,000 to more than 100,000 yuan (prices may fluctuate due to exchange rates). Generic drugs of Seputinib have also been put on the market for sale overseas, and their pharmaceutical ingredients are basically the same as those of the original drugs sold domestically and abroad. For example, the price of 40mg*120 capsules produced by a Laos pharmaceutical factory is more than RMB 4,000 per box (the price may fluctuate due to exchange rates).