Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial

Drilon, A; Subbiah, V; Gautschi, O; Tomasini, P; de Braud, F; Solomon, BJ; Shao-Weng Tan, D; Alonso, G; Wolf, J; Park, K; Goto, K; Soldatenkova, V; Szymczak, S; Barker, SS; Puri, T; Bence Lin, A; Loong, H; Besse, B

Author(s): Drilon, A; Subbiah, V; Gautschi, O; Tomasini, P; de Braud, F; Solomon, BJ; Shao-Weng Tan, D; Alonso, G; Wolf, J; Park, K; Goto, K; Soldatenkova, V; Szymczak, S; Barker, SS; Puri, T; Bence Lin, A; Loong, H; Besse, B;
Details: Publication Year 2023,Volume 41,Issue #2,Page 385-394
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: PURPOSE: Selpercatinib, a first-in-class, highly selective, and potent CNS-active RET kinase inhibitor, is currently approved for the treatment of patients with RET fusion-positive non-small-cell lung cancer (NSCLC). We provide a registrational data set update in more than double (n = 316) of the original reported population (n = 144) and better characterization of long-term efficacy and safety. METHODS: Patients were enrolled to LIBRETTO-001, a phase I/II, single-arm, open-label study of selpercatinib in patients with RET-altered cancers. An analysis of patients with RET fusion-positive NSCLC, including 69 treatment-naive and 247 with prior platinum-based chemotherapy, was performed. The primary end point was objective response rate (ORR; RECIST v1.1, independent review committee). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival, and safety. RESULTS: In treatment-naive patients, the ORR was 84% (95% CI, 73 to 92); 6% achieved complete responses (CRs). The median DoR was 20.2 months (95% CI, 13.0 to could not be evaluated); 40% of responses were ongoing at the data cutoff (median follow-up of 20.3 months). The median PFS was 22.0 months; 35% of patients were alive and progression-free at the data cutoff (median follow-up of 21.9 months). In platinum-based chemotherapy pretreated patients, the ORR was 61% (95% CI, 55 to 67); 7% achieved CRs. The median DoR was 28.6 months (95% CI, 20.4 to could not be evaluated); 49% of responses were ongoing (median follow-up of 21.2 months). The median PFS was 24.9 months; 38% of patients were alive and progression-free (median follow-up of 24.7 months). Of 26 patients with measurable baseline CNS metastasis by the independent review committee, the intracranial ORR was 85% (95% CI, 65 to 96); 27% were CRs. In the full safety population (n = 796), the median treatment duration was 36.1 months. The safety profile of selpercatinib was consistent with previous reports. CONCLUSION: In a large cohort with extended follow-up, selpercatinib continued to demonstrate durable and robust responses, including intracranial activity, in previously treated and treatment-naive patients with RET fusion-positive NSCLC.
Publisher: American Society of Clinical Oncology
Keywords: Humans; *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics; *Lung Neoplasms/drug therapy/genetics; Pyridines; Pyrazoles/therapeutic use; Protein Kinase Inhibitors/adverse effects; Proto-Oncogene Proteins c-ret/genetics
Department(s): Medical Oncology
PubMed ID: 36122315
Publisher's Version: https://doi.org/10.1200/JCO.22.00393
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-04-06 06:53:45

Last Modified: 2024-07-09 06:20:44