Selpercatinib in RET fusion-positive non-small-cell lung cancer (SIREN): a retrospective analysis of patients treated through an access program

Oliver Illini, Maximilian Johannes Hochmair, Hannah Fabikan, Christoph Weinlinger, Amanda Tufman, Aurélie Swalduz, Kristina Lamberg, Sayed M. S. Hashemi, Florian Huemer, Anders Vikström, Martin Wermke, Gudrun Absenger, Alfredo Addeo, Shantanu Banerji, Antonio Calles, Stephen Clarke, Massimo di Maio, Alice Durand, Michaël Duruisseaux, Malinda ItchinsOkko-Sakari Kääränien, Florian Krenn, Eckart Laack, Adrianus Johannes de Langen, Katja Mohorcic, Georg Pall, Antonio Passaro, Gerald Prager, Achim Rittmeyer, Jeffrey Rothenstein, Michael Schumacher, Ewald Wöll, Arschang Valipour

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18 Citations (Scopus)


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 fusion-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.
Original languageEnglish
JournalTherapeutic advances in medical oncology
Publication statusPublished - 2021


  • RET gene fusions
  • non-small cell lung cancer (NSCLC)
  • real-world data
  • selpercatinib
  • targeted therapy
  • tyrosine kinase inhibitor (TKI)

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