TY - JOUR
T1 - Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement
T2 - Results from the EUROS1 cohort
AU - Mazières, Julien
AU - Rouvière, Damien
AU - D.Milia, Julie
AU - Filleron, Thomas
AU - Zalcman, Gérard
AU - Biondani, Pamela
AU - Besse, Benjamin
AU - Barlesi, Fabrice
AU - Léna, Hervé
AU - Monnet, Isabelle
AU - Thiberville, Luc
AU - Pecuchet, Nicolas
AU - Crinò, Lucio
AU - Cappuzzo, Federico
AU - Dingemans, Anne Marie C.
AU - Smit Sacha I Rothschild, Egbert F.
AU - Spirig, Christian
AU - Diebold, Joachim
AU - Gautschi, Oliver
AU - Dziadziuszko, Rafal
AU - Wolf, Jurgen
AU - Thomas, Roman K.
AU - Leenders, Frauke
AU - Heuckmann, Johannes M.
N1 - Publisher Copyright:
© 2015 by American Society of Clinical Oncology.
PY - 2015/3/20
Y1 - 2015/3/20
N2 - Purpose Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains. Patients and Methods In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. Eligible patients had stage IV lung adenocarcinoma, had ROS1 rearrangement according to fluorescent in situ hybridization, and had received crizotinib therapy through an individual off-label use. Best response was assessed locally using RECIST (version 1.1). All other data were analyzed centrally. Results We identified 32 eligible patients. One patient was excluded because next-generation sequencing was negative for ROS1 fusion. Median age was 50.5 years, 64.5% of patients were women, and 67.7% were never-smokers. Thirty patients were evaluable for progressionfree survival (PFS), and 29 patients were evaluable for best response. We observed four patients with disease progression, two patients with stable disease, and objective response in 24 patients, including five complete responses (overall response rate, 80%; disease control rate, 86.7%). Median PFS was 9.1 months, and the PFS rate at 12 months was 44%. No unexpected adverse effects were observed. Twenty-six patients received pemetrexed (either alone or in combination with platinum and either before or after crizotinib) and had a response rate of 57.7% and a median PFS of 7.2 months. Conclusion Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned.
AB - Purpose Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains. Patients and Methods In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. Eligible patients had stage IV lung adenocarcinoma, had ROS1 rearrangement according to fluorescent in situ hybridization, and had received crizotinib therapy through an individual off-label use. Best response was assessed locally using RECIST (version 1.1). All other data were analyzed centrally. Results We identified 32 eligible patients. One patient was excluded because next-generation sequencing was negative for ROS1 fusion. Median age was 50.5 years, 64.5% of patients were women, and 67.7% were never-smokers. Thirty patients were evaluable for progressionfree survival (PFS), and 29 patients were evaluable for best response. We observed four patients with disease progression, two patients with stable disease, and objective response in 24 patients, including five complete responses (overall response rate, 80%; disease control rate, 86.7%). Median PFS was 9.1 months, and the PFS rate at 12 months was 44%. No unexpected adverse effects were observed. Twenty-six patients received pemetrexed (either alone or in combination with platinum and either before or after crizotinib) and had a response rate of 57.7% and a median PFS of 7.2 months. Conclusion Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned.
UR - http://www.scopus.com/inward/record.url?scp=84927139647&partnerID=8YFLogxK
U2 - 10.1200/JCO.2014.58.3302
DO - 10.1200/JCO.2014.58.3302
M3 - Article
C2 - 25667280
AN - SCOPUS:84927139647
SN - 0732-183X
VL - 33
SP - 992
EP - 999
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -
