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
| Autor: | Alexander Drilon, Vivek Subbiah, Oliver Gautschi, Pascale Tomasini, Filippo de Braud, Benjamin J. Solomon, Daniel Shao-Weng Tan, Guzmán Alonso, Jürgen Wolf, Keunchil Park, Koichi Goto, Victoria Soldatenkova, Sylwia Szymczak, Scott S. Barker, Tarun Puri, Aimee Bence Lin, Herbert Loong, Benjamin Besse |
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| Přispěvatelé: | Institut Català de la Salut, [Drilon A] Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY. [Subbiah V] The University of Texas MD Anderson Cancer Center, Houston, TX. [Gautschi O] University of Berne and Cantonal Hospital of Lucerne, Lucerne, Switzerland. [Tomasini P] Hôpitaux Universitaires, de Marseille Timone, France. [de Braud F] University of Milan, Milan, Italy. [Solomon BJ] Peter MacCallum Cancer Center, Melbourne, Australia. [Alonso G] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Cancer Research
Otros calificadores::Otros calificadores::/genética [Otros calificadores] Otros calificadores::/uso terapéutico [Otros calificadores] Medicaments antineoplàstics - Ús terapèutic acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos [COMPUESTOS QUÍMICOS Y DROGAS] diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Pulmons - Càncer - Aspectes genètics Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES] neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES] Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Oncology Avaluació de resultats (Assistència sanitària) Other subheadings::Other subheadings::/genetics [Other subheadings] Other subheadings::/therapeutic use [Other subheadings] Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [CHEMICALS AND DRUGS] Pulmons - Càncer - Tractament |
| Zdroj: | Scientia |
| Popis: | Selpercatinib; Lung cancer; Safety Selpercatinib; Cáncer de pulmón; Seguridad Selpercatinib; Càncer de pulmó; Seguretat 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. Supported by Loxo Oncology, a wholly owned subsidiary of Eli Lilly and Company. A.D. was supported in part by funding from the National Cancer Institute of the National Institutes of Health: 1R01CA251591- 01A1 and P30 CA008748. Partial support was likewise provided by LUNGevity. |
| Databáze: | OpenAIRE |
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