20.500.12556/DiRROS-14130 Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN) : a retrospective analysis of patients treated through an access program Introduction: 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. non-small cell lung carcinoma -- drug therapy -- genetics molecular targeted therapy real-world data selpercatinib targeted therapy tyrosine kinase inhibitor nedrobnocelični karcinom pljuč -- terapija z zdravili -- genetika molekularna tarčna terapija podatki iz resničnega življenja selperactinib tarčna terapija zaviralci tirozinskih kinaz true false true Sage Journals Angleški jezik Ni določen © The Author(s), 2021. Neznano 2021-06-16 13:50:17 2021-06-16 13:50:18 2022-08-19 03:39:10 0000-00-00 00:00:00 2021 0 Velika Britanija 0 Nasl. z nasl. zaslona; Soavtorica iz Slovenije: Katja Mohorčič; Opis vira z dne 14. 6. 2021; str. 1-17 Vol. 13 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-006 1758-8359 10.1177/17588359211019675 66935555 RAZ_Illini_Oliver_i2021.pdf RAZ_Illini_Oliver_i2021.pdf 1 4E4A25935572544E10543B5761550F3C c74599c868d7bb8698aed53637ff988ab403a9461b90963ac59706253aea6613 975935f4-17b6-11ed-b6b8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=17529 RAZ_Illini_Oliver_i2021.pdf RAZ_Illini_Oliver_i2021.pdf 1 FEC0A24230BF6F365D92D0FF838F908C a63e02a07dbb68b3bf8190cdee830aa0c680cea7e738f48dc43406f568ed2b70 976c48b8-17b6-11ed-b6b8-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=17530 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0