Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN) : a retrospective analysis of patients treated through an access programIllini, Oliver (Avtor) Hochmair, Maximilian J (Avtor) Fabikan, Hannah (Avtor) Weinlinger, Christoph (Avtor) Tufman, Amanda (Avtor) Swalduz, Aurélie (Avtor) Lamberg, Kristina (Avtor) Hashemi, Sayed M. S. (Avtor) Huemer, Florian (Avtor) Vikström, Anders (Avtor) Mohorčič, Katja (Avtor) non-small cell lung carcinoma -- drug therapy -- geneticsmolecular targeted therapyreal-world dataselpercatinibtargeted therapytyrosine kinase inhibitorIntroduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusio-%positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases (n=8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade >/=3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.Sage Journals20212021-06-16 13:50:17Neznano14130UDK: 616-006ISSN pri članku: 1758-8359DOI: 10.1177/17588359211019675COBISS_ID: 66935555sl© The Author(s), 2021.