Targeting RET in patients with RET-rearranged lung cancers: Results from the global, multicenter RET registry
Journal
Journal of Clinical Oncology
Journal Volume
35
Journal Issue
13
Pages
1403-1410
Date Issued
2017
Author(s)
Gautschi O.
Milia J.
Filleron T.
Wolf J.
Carbone D.P.
Owen D.
Camidge R.
Narayanan V.
Doebele R.C.
Besse B.
Remon-Masip J.
Janne P.A.
Awad M.M.
Peled N.
Byoung C.-C.
Karp D.D.
Van Den Heuvel M.
Wakelee H.A.
Neal J.W.
Mok T.S.K.
Ou S.-H.I.
Pall G.
Froesch P.
Zalcman G.
Gandara D.R.
Riess J.W.
Velcheti V.
Zeidler K.
Diebold J.
Früh M.
Michels S.
Monnet I.
Popat S.
Rosell R.
Karachaliou N.
Rothschild S.I.
Warth A.
Muley T.
Cabillic F.
Mazières J.
Drilon A.
Abstract
Purpose: In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods: A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or nextgeneration sequencing. Anonymized data-clinical, pathologic, and molecular features-were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. Results: By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). Conclusion: Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients. ? 2017 by American Society of Clinical Oncology.
SDGs
Other Subjects
alectinib; cabozantinib; lenvatinib; nintedanib; ponatinib; protein Ret; regorafenib; sorafenib; sunitinib; vandetanib; antineoplastic agent; protein kinase inhibitor; protein Ret; RET protein, human; adult; aged; Article; cancer combination chemotherapy; cancer survival; disease course; enzyme inhibition; female; gene rearrangement; human; in situ hybridization; major clinical study; male; next generation sequencing; non small cell lung cancer; outcome assessment; overall survival; patient selection; priority journal; progression free survival; real time polymerase chain reaction; retrospective study; reverse transcription polymerase chain reaction; antagonists and inhibitors; Carcinoma, Non-Small-Cell Lung; clinical trial; enzymology; genetics; international cooperation; Lung Neoplasms; middle aged; molecularly targeted therapy; multicenter study; prospective study; register; treatment outcome; very elderly; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Gene Rearrangement; Humans; International Cooperation; Lung Neoplasms; Middle Aged; Molecular Targeted Therapy; Prospective Studies; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-ret; Registries; Treatment Outcome
Publisher
American Society of Clinical Oncology
Type
journal article