RT Journal Article
T1 Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial.
A1 Michels, Sebastian
A1 Massutí, Bartomeu
A1 Schildhaus, Hans-Ulrich
A1 Franklin, Jeremy
A1 Sebastian, Martin
A1 Felip, Enriqueta
A1 Grohé, Christian
A1 Rodriguez-Abreu, Delvys
A1 Abdulla, Diana S Y
A1 Bischoff, Helge
A1 Brandts, Christian
A1 Carcereny, Enric
A1 Corral, Jesús
A1 Dingemans, Anne-Marie C
A1 Pereira, Eva
A1 Fassunke, Jana
A1 Fischer, Rieke N
A1 Gardizi, Masyar
A1 Heukamp, Lukas
A1 Insa, Amelia
A1 Kron, Anna
A1 Menon, Roopika
A1 Persigehl, Thorsten
A1 Reck, Martin
A1 Riedel, Richard
A1 Rothschild, Sacha I
A1 Scheel, Andreas H
A1 Scheffler, Matthias
A1 Schmalz, Petra
A1 Smit, Egbert F
A1 Limburg, Meike
A1 Provencio, Mariano
A1 Karachaliou, Niki
A1 Merkelbach-Bruse, Sabine
A1 Hellmich, Martin
A1 Nogova, Lucia
A1 Büttner, Reinhard
A1 Rosell, Rafael
A1 Wolf, Jürgen
K1 Crizotinib
K1 Lung cancer
K1 ROS1
K1 TP53
K1 Targeted treatment
AB ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients.
YR 2019
FD 2019-04-09
LK http://hdl.handle.net/10668/13819
UL http://hdl.handle.net/10668/13819
LA en
DS RISalud
RD Apr 7, 2025