RET fusion-positive non-small-cell lung cancer (NSCLC) patients can now get therapy with selpercatinib, a first-in-class, powerful, highly selective, and CNS-active RET kinase inhibitor. To further characterize long-term effectiveness and safety, researchers presented a registrational data set update in a cohort that was more than twice as large (n = 316) as the initial reported sample (n = 144).

Participants were accepted into LIBRETTO-001, a phase I/II, single-arm, open-label research of selpercatinib in people with malignancies that have RET mutations. An examination of patients with NSCLC that had RET fusion was done, comprising 247 patients who had previously received platinum-based chemotherapy and 69 treatment-naive patients. The objective response rate (ORR; RECIST v1.1, independent review committee) was the main outcome measure. Other endpoints were safety, overall survival, progression-free survival (PFS), and duration of response (DoR).

The ORR was 84% (95% CI, 73 to 92) in treatment-naive patients, and 6% of them had complete responses (CRs). A total of 40% of replies were still being processed at the time of the data cutoff, with a median DoR of 20.2 months (95% CI, 13.0 to could not be assessed) (median follow-up of 20.3 months). The median PFS was 22.0 months, and at the data cutoff, 35% of patients were still alive and not progressing (median follow-up of 21.9 months). Patients who had had prior platinum-based chemotherapy had an ORR of 61% (95% CI, 55 to 67); 7% of them had CRs. 49% of responses were continuing, and the median DoR was 28.6 months (95% CI, 20.4 to could not be assessed) (median follow-up of 21.2 months). 38% of patients were still alive and without progression at the median PFS of 24.9 months (median follow-up of 24.7 months). The intracranial ORR was 85% (95% CI, 65 to 96) of the 26 patients with detectable baseline CNS metastases according to the independent review committee, 27% of whom were CRs. The median treatment time in the complete safety population (n = 796) was 36.1 months. Selpercatinib’s safety profile matched up with earlier data.

Selpercatinib continued to show robust and persistent responses, including intracranial activity, in both previously treated and treatment-naive patients with RET fusion-positive NSCLC in a large cohort with extended follow-up.