Therapeutic Advances in Medical Oncology (Jun 2021)

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 Itchins,
  • Okko-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

DOI
https://doi.org/10.1177/17588359211019675
Journal volume & issue
Vol. 13

Abstract

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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.