Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancer: Final Safety and Efficacy, Including Overall Survival, From the LIBRETTO-001 Phase I/II Trial

Gautschi, O; de Braud, F; Park, K; Solomon, BJ; Tomasini, P; Loong, HH; Goto, K; Peterson, P; Barker, S; Liming, K; Oxnard, GR; Frimodt-Moller, B; Drilon, A

Author(s): Gautschi, O; de Braud, F; Park, K; Solomon, BJ; Tomasini, P; Loong, HH; Goto, K; Peterson, P; Barker, S; Liming, K; Oxnard, GR; Frimodt-Moller, B; Drilon, A;
Details: Publication Year 2025-05-20,Volume 43,Issue #15,Page 1758-1764
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: LIBRETTO-001 (ClinicalTrials.gov identifier: NCT03157128) is a registrational phase I/II, single-arm, open-label trial of selpercatinib in RET-dependent cancers. With 19 months of additional follow-up, we report the final efficacy and safety results of selpercatinib in patients with RET fusion-positive non-small cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy (N = 247) or were treatment-naïve (N = 69). The objective response rate (ORR) was 62% for pretreated patients and 83% for treatment-naïve patients. Duration of response (DoR) was 31.6 months for pretreated and 20.3 months for treatment-naïve patients (median follow-up approximately 38 months). Median progression-free survival (PFS) was 26.2 months for pretreated and 22.0 months for treatment-naïve patients (median follow-up approximately 40 months). Median overall survival was 47.6 months in pretreated patients and was not reached in the treatment-naïve group (median follow-up approximately 43 months). At the 3-year landmark estimate, 57% of pretreated and 66% of treatment-naïve patients were alive. Among 26 patients with measurable CNS metastases at baseline, the CNS-ORR was 85% with a CNS-DoR of 9.4 months and CNS-PFS of 11.0 months. The safety profile of selpercatinib was consistent with previous reports. With substantial additional follow-up, selpercatinib continued to show durable responses and intracranial activity, with a manageable safety profile in patients with RET fusion-positive NSCLC.
Publisher: American Society of Clinical Oncology
Keywords: Humans; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/mortality/pathology; *Lung Neoplasms/drug therapy/genetics/pathology/mortality; Male; Female; Middle Aged; *Proto-Oncogene Proteins c-ret/genetics; Aged; Adult; *Pyrazoles/therapeutic use/adverse effects; *Pyridines/therapeutic use/adverse effects; *Oncogene Proteins, Fusion/genetics; *Protein Kinase Inhibitors/therapeutic use/adverse effects; Progression-Free Survival; Aged, 80 and over
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1200/jco-24-02076
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-03-18 06:23:42

Last Modified: 2025-06-02 01:58:43