Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial
Michels, Sebastian (Universität zu Köln)
Massutí, Bartomeu (Hospital Universitari d'Alacant (País Valencià))
Vasyliv, I. (Universität zu Köln)
Stratmann, Jan Alexander (University Hospital of Frankfurt (Alemanya))
Frank, Julia (Universität zu Köln)
Adams, Anne (Universität zu Köln)
Felip, Enriqueta (Vall d'Hebron Institut d'Oncologia)
Grohé, Christian (Evangelische Lungenklinik Berlin (Alemanya))
Rodríguez-Abreu, Delvys (Complejo Hospitalario Universitario Insular Materno Infantil (Las Palmas de Gran Canaria))
Bischoff, Helger G. (Thoraxonkologie. Thoraxklinik (Heidelberg, Alemanya))
Carcereny, Enric (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Corral, Jesús M. (Clínica Universidad de Navarra)
Pereira, Eva (Grupo Español de Cáncer de Pulmón (Barcelona, Catalunya))
Fassunke, Jana (Universität zu Köln)
Fischer, Rieke Nila (Universität zu Köln)
Insa, Amelia (Hospital Clínic Universitari (València))
Koleczko, Sophia (Universität zu Köln)
Nogova, Lucia (Universität zu Köln)
Reck, Martin (German Center for Lung Research (Großhansdorf, Alemanya))
Reutter, Theresa (Asklepios Clinic Altona (Hamburg, Alemanya))
Riedel, Richard (Universität zu Köln)
Schaufler, Diana (Universität zu Köln)
Scheffler, Matthias (Universität zu Köln)
Weisthoff, Mathilda (Universität zu Köln)
Provencio Pulla, Mariano (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Merkelbach-Bruse, Sabine (Universität zu Köln)
Hellmich, Martin (Universität zu Köln)
Sebastian, Martin (University Hospital of Frankfurt (Alemanya))
Büttner, Reinhard H. (Universität zu Köln)
Persigehl, Thorsten (Universität zu Köln)
Rosell, Rafael (Institut Germans Trias i Pujol)
Wolf, Jürgen (Universität zu Köln)

Data:	2024
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Lung cancer ; ROS1 ; Crizotinib ; Overall survival ; EUCROSS
Publicat a:	ESMO open, Vol. 9 Núm. 2 (february 2024) , p. 102237, ISSN 2059-7029

DOI: 10.1016/j.esmoop.2024.102237
PMID: 38350336

10 p, 517.5 KB

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