Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial

Background: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we...

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Autores: Michels, Sebastian|||0000-0003-3164-870X, Massutí, Bartomeu|||0000-0002-7608-3952, Vasyliv, I., Stratmann, Jan Alexander, Frank, Julia, Adams, Anne, Felip, Enriqueta|||0000-0002-7620-0098, Grohé, Christian, Rodríguez-Abreu, Delvys|||0000-0003-0506-1366, Bischoff, Helger G., Carcereny, Enric|||0000-0001-5235-5602, Corral, Jesús M., Pereira, Eva, Fassunke, Jana, Fischer, Rieke Nila, Insa, Amelia|||0000-0002-3438-6170, Koleczko, Sophia, Nogova, Lucia|||0000-0002-4502-1812, Reck, Martin|||0000-0002-5348-4462, Reutter, Theresa, Riedel, Richard, Schaufler, Diana, Scheffler, Matthias|||0000-0002-9031-1368, Weisthoff, Mathilda|||0000-0001-6536-3898, Provencio Pulla, Mariano|||0000-0001-6315-7919, Merkelbach-Bruse, Sabine, Hellmich, Martin|||0000-0001-5174-928X, Sebastian, Martin|||0000-0002-0404-7741, Büttner, Reinhard H., Persigehl, Thorsten|||0000-0001-5928-4405, Rosell, Rafael|||0000-0003-0817-3400, Wolf, Jürgen
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:311108
Acceso en línea:https://ddd.uab.cat/record/311108
https://dx.doi.org/urn:doi:10.1016/j.esmoop.2024.102237
Access Level:acceso abierto
Palabra clave:Lung cancer
ROS1
Crizotinib
Overall survival
EUCROSS
Descripción
Sumario:Background: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. Materials and methods: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. Results: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. Conclusions: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

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