Aims: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor with CNS activity, is approved in multiple countries for the treatment of RET-mutant MTC and RET fusion-positive solid tumors, including lung and thyroid, and has previously been reported to be well tolerated.
Methods: Updated analysis of selpercatinib in patients with RET fusion-positive systemic treatment-naive thyroid cancer (TC), after RAI (where RAI appropriate) in LIBRETTO-001 (NCT03157128) was conducted after median follow-up for overall survival (OS) of 56.3 months. Primary endpoint was objective response rate (ORR, RECIST 1.1) by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression free survival (PFS), and safety.
Results: Of the 24 patients with TC that received first-line selpercatinib, 58.3% were male with a median age of 60.5 years. First line patients achieved an ORR by RECIST 1.1 of 95.8%(95%CI:78.9-99.9) based on IRC. The 5-year estimated DoR rate was 63.5% (95%CI:31.3-83.7) with median not estimable at 54.8-months follow up (95%CI:42.8-NE). The 5-year estimated PFS rate was 70.7% (95%CI:42.3-87.0) with median not estimable at 58.6-months follow up(95%CI:44.6-NE). The 5-year estimated OS rate was 75.7%(95%CI:45.8-90.6) with median OS not estimable (95%CI:56.4-NE). In the safety population (N= 24), no new safety signals were identified compared to previous reports. Ten patients required a dose modification and no patient discontinued treatment due to TEAEs.
Conclusions: With longer follow-up selpercatinib continues to demonstrate durable responses and strong 5-year rates of PFS and OS in patients with RET-fusion systemic treatment-naive thyroid cancer, further highlighting selpercatinib as the standard of care for the first line treatment of RET-fusion TC. The safety remained tolerable despite longer duration on treatment. Testing for RET-fusion in TC before systemic therapy should be done to identify who can benefit from selpercatinib treatment.