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 Journal Article
| Authors: | Gautschi, O.; Park, K.; Solomon, B. J.; Tomasini, P.; Loong, H. H.; De Braud, F.; Goto, K.; Peterson, P.; Barker, S.; Liming, K.; Oxnard, G. R.; Frimodt-Moller, B.; Drilon, A. |
| Article Title: | 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 |
| 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. © 2025 American Society of Clinical Oncology. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; genetics; clinical trial; mortality; pyridines; progression free survival; phase 2 clinical trial; protein kinase inhibitor; carcinoma, non-small-cell lung; lung neoplasms; pathology; protein kinase inhibitors; lung tumor; pyrazole derivative; multicenter study; pyrazoles; oncogene proteins, fusion; phase 1 clinical trial; drug therapy; protein ret; ret protein, human; proto-oncogene proteins c-ret; pyridine derivative; non small cell lung cancer; progression-free survival; very elderly; humans; human; male; female; selpercatinib; oncogene fusion protein |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 15 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-05-20 |
| Start Page: | 1758 |
| End Page: | 1764 |
| Language: | English |
| DOI: | 10.1200/jco-24-02076 |
| PUBMED: | 39983053 |
| PROVIDER: | scopus |
| PMCID: | PMC12084017 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Alexander Drilon -- Source: Scopus |
