Author/Editor		Illini, Oliver; Hochmair, Maximilian J; Fabikan, Hannah; Weinlinger, Christoph; Tufman, Amanda; Swalduz, Aurélie; Lamberg, Kristina; Hashemi, Sayed M. S.; Huemer, Florian; Vikström, Anders; Mohorčič, Katja
Title		Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN)
Type		članek
Vol. and No.		, št. Vol. 13
Publication year		2021
Volume		str. 1-17
ISSN		1758-8359 - Therapeutic advances in medical oncology
Language		eng
Abstract		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.
Descriptors		Carcinoma, non-small cell lung Molecular targeted therapy Nedrobnocelični karcinom pljuč Molekularna tarčna terapija Drug therapy Genetics Terapija z zdravili Genetika
Keywords		podatki iz resničnega življenja selperactinib tarčna terapija zaviralci tirozinskih kinaz real-world data selpercatinib targeted therapy tyrosine kinase inhibitor