Global RET Registry (GLORY): Activity of RET-Directed Targeted Therapies in RET-Rearranged Lung Cancers
Invited conference paper presented and published in conference proceedings


摘要Background: GLORY is a global registry of patients with RET-rearranged non-small cell lung cancer (NSCLC). In
order to complement ongoing prospective studies, the registry’s goal is to provide data on the efficacy of RETdirected
targeted therapies administered outside the context of a clinical trial. We previously reported results from our first interim analysis (Gautschi, ASCO 2016). Following additional accrual into the registry, updated results are presented here, with a focus on an expanded efficacy analysis of various RET inhibitors.

Methods: A global, multicenter network of thoracic oncologists identified patients with pathologically-confirmed
NSCLC harboring a RET rearrangement. Molecular profiling was performed locally via RT-PCR, FISH, or next-generation sequencing. Anonymized data including clinical, pathologic, and molecular features were collected centrally and analyzed by an independent statistician. Response to RET tyrosine kinase inhibition (TKI) administered off-protocol was determined by RECIST1.1 (data cutoff date: April 15, 2016). In the subgroup of patients who received RET TKI therapy, the objectives were to determine overall response rate (ORR, primary objective), progression-free survival (PFS), and overall survival (OS).

Results: 165 patients with RET-rearranged NSCLC from 29 centers in Europe, Asia, and the USA were accrued. The
median age was 61 years (range 28-89 years). The majority of patients were female (52%), never smokers (63%), with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent metastasic sites were lymph nodes (82%), bone (51%) and lung (32%). KIF5B-RET was the most commonly identified fusion (70%). 53 patients
received at least one RET-TKI outside of a clinical protocol, including cabozantinib (21), vandetanib (11), sunitinib
(10), sorafenib (2), alectinib (2), lenvatinib (2), nintedanib (2), ponatinib (2) and regorafenib (1). In patients who were
evaluable for response (n¼50), the ORR was 37% for cabozantinib, 18% for vandetanib, and 22% for sunitinib. Median PFS was 3.6, 2.9, and 2.2 months and median OS was 4.9, 10.2, and 6.8 months for cabozantinib, vandetanib, and sunitinib, respectively. Responses were also observed with nintedanib and lenvatinib. Among patients who received more than one TKI (n¼10), 3 partial responses were achieved after prior treatment with a different TKI.

Conclusion: RET inhibitors are active in individual patients with RET-rearranged NSCLC, however, novel
therapeutic approaches are warranted with the hope of improving current clinical outcomes. GLORY remains the
largest dataset of patients with RET-rearranged NSCLC, and continues to accrue patients.
著者Oliver Gautschi, Julie Milia-Baron, Thomas Filleron, Jürgen Wolf, David Carbone, Dwight Owen, D. Ross Camidge,
Vighesh Narayanan, Robert Doebele, Benjamin Besse, Jordi Remon, Pasi Jänne,Mark Awad, Nir Peled, Chul-Cho Byoung,Daniel Karp, Michael Van Den Heuvel, Heather Wakelee, Joel Neal, Tony Mok,James Chih-Hsin Yang, Sai-Hong Ou, Georg Pall,Patrizia Froesch, Gérard Zalcman,David R. Gandara, Jonathan Riess,Vamsidhar Velcheti, Kristin Zeidler,Joachim Diebold, Martin Früh, Sebastian Michels,Isabelle Monnet, Sanjay Popat, Rafael Rosell,
Niki Karachaliou, Sacha Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley,Florian Cabillic, Julien Mazieres,
Alexander Drilon
會議名稱IASLC 17th World Conference on Lung Cancer Dec 4-7, 2016
期刊名稱Journal of Thoracic Oncology
會議論文集題名Journal of Thoracic Oncology
出版社Lippincott, Williams & Wilkins
關鍵詞lung cancers

上次更新時間 2020-09-07 於 02:19