TY - JOUR
T1 - Targeting RET in patients with RET-rearranged lung cancers
T2 - Results from the global, multicenter RET registry
AU - Gautschi, Oliver
AU - Milia, Julie
AU - Filleron, Thomas
AU - Wolf, Juergen
AU - Carbone, David P.
AU - Owen, Dwight
AU - Camidge, Ross
AU - Narayanan, Vignhesh
AU - Doebele, Robert C.
AU - Besse, Benjamin
AU - Remon-Masip, Jordi
AU - Janne, Pasi A.
AU - Awad, Mark M.
AU - Peled, Nir
AU - Byoung, Chul Cho
AU - Karp, Daniel D.
AU - Van Den Heuvel, Michael
AU - Wakelee, Heather A.
AU - Neal, Joel W.
AU - Mok, Tony S.K.
AU - Yang, James C.H.
AU - Ou, Sai Hong Ignatius
AU - Pall, Georg
AU - Froesch, Patrizia
AU - Zalcman, Gérard
AU - Gandara, David R.
AU - Riess, Jonathan W.
AU - Velcheti, Vamsidhar
AU - Zeidler, Kristin
AU - Diebold, Joachim
AU - Früh, Martin
AU - Michels, Sebastian
AU - Monnet, Isabelle
AU - Popat, Sanjay
AU - Rosell, Rafael
AU - Karachaliou, Niki
AU - Rothschild, Sacha I.
AU - Shih, Jin Yuan
AU - Warth, Arne
AU - Muley, Thomas
AU - Cabillic, Florian
AU - Mazières, Julien
AU - Drilon, Alexander
N1 - Publisher Copyright:
© 2017 by American Society of Clinical Oncology.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85018282184&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.70.9352
DO - 10.1200/JCO.2016.70.9352
M3 - Article
C2 - 28447912
AN - SCOPUS:85018282184
SN - 0732-183X
VL - 35
SP - 1403
EP - 1410
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 13
ER -
