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Original article: Central nervous system disease in patients with RET fusion-positive non-small cell lung cancer treated with selpercatinib

Open AccessPublished:January 16, 2023DOI:https://doi.org/10.1016/j.jtho.2023.01.008
Original article: Central nervous system disease in patients with RET fusion-positive non-small cell lung cancer treated with selpercatinib
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      ABSTRACT

      Background

      Central nervous system (CNS) metastases develop in nearly half of patients and cause morbidity and mortality in RET fusion-positive non-small cell lung cancers (NSCLCs). The selective RET inhibitor selpercatinib treats existing intracranial disease, but no studies have investigated whether early initiation of selpercatinib is associated with decreased development of CNS metastases.

      Patients and methods

      Sixty-one patients with RET fusion-positive advanced NSCLC with and without CNS metastases treated with selpercatinib on the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 expanded access program (EAP, NCT03906331) were identified. Cumulative incidence rates (CIRs) for CNS metastases were assessed as an event-of-interest; systemic progression of disease and death were considered competing risks.

      Results

      The median age was 65 years, and the most common 5’ fusion partners were KIF5B (67%) and CCDC6 (18%). Twenty-four patients (39%) received prior platinum chemotherapy; twenty patients (33%) received prior multikinase inhibition. The median time on selpercatinib was 21.8 months. Thirty patients (49%) had CNS disease at baseline, and thirty-one patients (51%) had no baseline CNS disease. CIRs of CNS progression among patients with baseline CNS disease were 3% (95% CI: 0-10%), 10% (95% CI: 0-22%), 17% (3-30%), 17% (3-30%), and 20% (5-35%) at 6, 12, 18, 24, and 36 months, respectively. CIRs for CNS progression among patients without baseline CNS disease were 0% at 6, 12, 18, 24, and 36 months (95% CI: 0-0%).

      Conclusions

      CNS progression was not observed with selpercatinib therapy in patients without baseline CNS disease. CNS progression on selpercatinib was rare in patients with baseline CNS disease. Early initiation of selpercatinib is associated with decreased rates of CNS metastasis formation and progression, and may play a preventive role.

      Keywords

      Article info

      Publication history

      Accepted: January 6, 2023
      Received in revised form: January 2, 2023
      Received: November 21, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Author twitter handles: @yoninamg @alexdrilon @alexiaIasonos @sabs_lin @dazhiliurx

      Conflicts of Interest:

      Y.R. Murciano-Goroff reports travel, accommodation, and expenses from AstraZeneca and honoraria from Virology Education and Projects in Knowledge (for a CME program funded by an educational grant from Amgen). She acknowledges associated research funding to the institution from Loxo Oncology at Eli Lilly, Elucida Oncology, Taiho Oncology, Hengrui USA, Ltd/ Jiangsu Hengrui Pharmaceuticals, Luzsana Biotechnology, and Endeavor Biomedicines. She acknowledges royalties from Rutgers University Press and Wolters Kluwer. D. Liu reports consulting fees from Invitae. A. Iasonos reports royalties from Chapman and Hall, and consulting fees from Mirati (data safety and monitoring board) and Intelligencia (scientific advisor). A. Drilon reports Honoraria/Advisory Boards: Ignyta, Genentech, Roche, MORE Health, AXIS, Loxo, Eli Lilly and Company, Bayer, AbbVie, EPG Health, Takeda, Ariad, Millenium, 14ner, Elevation Oncology, Harborside Nexus, TP Therapeutics, ArcherDX, Liberum, AstraZeneca, Monopteros, RV More, Pfizer, Novartis, Ology, Blueprint Medicines, EMD Serono, Amgen, Helsinn, Medendi, TouchIME, BeiGene, Repare RX, Janssen, BergenBio, Nuvalent, Entos, Hengrui Therapeutics, Merus, Treeline Bio, Exelixis, Chugai Pharmaceutical, Prelude, Tyra Biosciences, Remedica Ltd, Applied Pharmaceutical Science, Inc., Verastem, mBrace, Treeline, MonteRosa, AXIS; Associated Research Paid to Institution: Pfizer, Exelixis, GlaxoSmithKlein, Teva, Taiho, PharmaMar; Royalties: Wolters Kluwer; Other (Food/Beverage): Merck, Puma, Merus, Boehringer Ingelheim; and CME Honoraria: Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, Research to Practice, Axis,Peerview Institute, Paradigm Medical Communications, WebMD, MJH Life Sciences, AXIS, EPG Health, JNCC/Harborside, I3 Health. The remaining authors have no disclosures to report.

      Identification

      DOI: https://doi.org/10.1016/j.jtho.2023.01.008

      Copyright

      © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

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